Astrocyte and endothelial cell expression of ADAM 17 (TACE) in adult human CNS

ADAM 17, also known as TACE, is an important sheddase for a number of proteins, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF-alpha), L-selectin, p75, and p55 TNF receptors, and interleukin-1 receptor II (IL-1RII). The presence of ADAM 17 mRNA in adult mouse and rat CNS was recently reported (Karkkainen et al. Mol Cell Neurosci 15:547-560, 2000). However, the cellular origin of ADAM 17 remains unknown. In this study, we have used an anti-ADAM 17 antibody in an immunohistochemical study of its distribution in human adult CNS tissue. Cells with astrocytic and endothelial morphology were ADAM 17-positive. This finding was further confirmed using double immunofluorescence with antibodies against GFAP and von Willebrand factor, which label astrocytes and endothelial cells, respectively. This study demonstrates that ADAM 17 is expressed by astrocytes and endothelial cells in normal brain tissue and may have a role in normal brain function.     

Measurement of betacellulin levels in bovine serum, colostrum and milk

Betacellulin, a member of the epidermal growth factor (EGF) family, was originally isolated and identified from the conditioned medium from a murine pancreatic beta-cell carcinoma cell line. Recently, we isolated bovine betacellulin from a growth factor enriched cheese whey extract, but there is no information on the presence of betacellulin in other biological fluids. We have cloned the cDNA for bovine betacellulin, produced recombinant betacellulin and shown that it has a similar potency to the purified native molecule in stimulating the proliferation of Balb/c3T3 fibroblasts. We have produced a polyclonal antiserum to bovine betacellulin which did not cross-react with EGF or transforming growth factor-alpha (TGF-alpha). The antibody was used in a homologous RIA that was able to detect betacellulin in pooled bovine colostrum sampled during the first 3 days after calving (2.30+/-0.11 ng/ml mean+/-s.e.m.; n=6), in bovine milk soluble fraction (1.93+/-0.64 ng/ml mean+/-s.e.m.; n=5) and in bovine cheese whey (2.59+/-0.16 ng/ml mean+/-s.e.m.; n=3). The betacellulin concentration in foetal bovine serum (FBS) (3.68+/-0.59 ng/ml mean+/-s.e.m.; n=6) greatly exceeded that of betacellulin in serum from male calves 1 and 5 weeks of age (0.53+/-0.15 ng/ml and 0.70+/- 0.09 ng/ml respectively; mean+/-s.e.m.; n=9). Betacellulin measured in the serum of these same animals when aged between 27 and 43 weeks was below the detection limits of the RIA. Sera from 10 out of 36 unmated heifers contained betacellulin levels within the detection limits of the assay (0.433+/-0.06 ng/ml mean+/-s.e.m.; n=10). The presence of betacellulin in bovine colostrum and milk suggests that it plays a role in the growth and development of the neonate and/or mammary gland function. The results also show that betacellulin is undetectable in the castrated adult male circulation. Additionally, although present in very low amounts, serum betacellulin could be under hormonal regulation in the female, since betacellulin was detected in sera from 27% of the unmated heifers examined in this study. The high levels of betacellulin detected in FBS relative to newborn and adult serum suggests a possible endocrine role for this growth factor in the bovine foetus.     

Reductions in occipital cortex GABA levels in panic disorder detected with 1h-magnetic resonance spectroscopy

BACKGROUND: There is preclinical evidence and indirect clinical evidence implicating gamma-aminobutyric acid (GABA) in the pathophysiology and treatment of human panic disorder. Specifically, deficits in GABA neuronal function have been associated with anxiogenesis, whereas enhancement of GABA function tends to be anxiolytic. Although reported peripheral GABA levels (eg, in cerebrospinal fluid and plasma) have been within reference limits in panic disorder, thus far there has been no direct assessment of brain GABA levels in this disorder. The purpose of the present work was to determine whether cortical GABA levels are abnormally low in patients with panic disorder. METHODS: Total occipital cortical GABA levels (GABA plus homocarnosine) were assessed in 14 unmedicated patients with panic disorder who did not have major depression and 14 retrospectively age- and sex-matched control subjects using spatially localized (1)H-magnetic resonance spectroscopy. All patients met DSM-IV criteria for a principal current diagnosis of panic disorder with or without agoraphobia. RESULTS: Patients with panic disorder had a 22% reduction in total occipital cortex GABA concentration (GABA plus homocarnosine) compared with controls. This finding was present in 12 of 14 patient-control pairs and was not solely accounted for by medication history. There were no significant correlations between occipital cortex GABA levels and measures of illness or state anxiety. CONCLUSIONS: Panic disorder is associated with reductions in total occipital cortex GABA levels. This abnormality might contribute to the pathophysiology of panic disorder.     

Computer assisted strain-gauge plethysmography is a practical method of excluding deep venous thrombosis

AIM: To evaluate a computed strain-gauge plethysmograph (CSGP) as a screening tool to exclude above knee deep venous thrombosis (DVT). METHODS: The first phase took place in the Radiology department. One hundred and forty-nine patients had both Doppler ultrasound and CSGP performed. Discordant results were resolved by venography where possible. The second phase took place in an acute medical admissions ward using a modified protocol. A further 173 patients had both studies performed. The results were collated and analysed. RESULTS: Phase 1. The predictive value of a negative CSGP study was 98%. There were two false-negative CSGP results (false-negative rate 5%), including one equivocal CSGP study which had deep venous thrombosis on ultrasound examination. Two patients thought to have thrombus on ultrasound proved not to have acute thrombus on venography. Phase 2. The negative predictive value of CSGP using a modified protocol was 97%. There were two definite and one possible false-negative studies (false-negative rate 4-7%). CONCLUSION: Computer strain-gauge plethysmograph can provide a simple, cheap and effective method of excluding lower limb DVT. However, its use should be rigorously assessed in each hospital in which it is used. Goddard, A. J. P., Chakraverty, S. & Wright, J. (2001). Clinical Radiology56, 30-34.     

Campylobacter 0:41 isolation in Guillain-Barré syndrome

Over a period of 15 months, 17 children were admitted to the Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town with Guillain-Barré syndrome. Stool specimens were collected from 14 children and campylobacter was isolated from nine. Six of the nine isolates of Campylobacter jejuni were further identified as C jejuni biotype 2, serotype 0:41. This biotype 2, serotype 0:41 has been identified in only 12 of the 7119 campylobacter isolates at the RCWMCH over a 19 year period. Eight of the nine patients with campylobacter isolates and one of five with negative stool cultures required ventilation. Patients with C jejuni biotype 2, serotype 0:41 were ventilated for a mean (SD) of 33.5 (19.4) days, whereas patients with other campylobacter isolates were ventilated for 17.3 (3.8) days. This is the first report of campylobacters of serotype 0:41 in Guillain-Barré syndrome and could reflect a geographical isolation of this strain.     

Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study

OBJECTIVES: To identify the risk factors for sudden infant death syndrome (SIDS) following a national campaign to prevent SIDS. METHODS: For 2 years (October 1, 1991 through September 30, 1993) data were collected by community child health nurses on all infants born in New Zealand at initial contact and at 2 months. RESULTS: There were 232 SIDS cases in the postneonatal age group (2.0/1000 live births) and these were compared with 1200 randomly selected control subjects. Information was available for 127 cases (54.7%) and 922 (76.8%) of controls. The previously identified modifiable risk factors were examined. The prevalence of prone sleeping position of the infant was very low (0.7% at initial contact and 3. 0% at 2 months), but was still associated with an increased risk of SIDS. In addition, the side sleeping position was also found to have an increased risk of SIDS compared with the supine sleeping position (at 2 months: adjusted odds ratio (OR) = 6.57; 95% confidence interval (CI) = 1.71, 25.23). Maternal smoking was found to be the major risk factor for SIDS. Bed sharing was also associated with an increased risk of SIDS. There was an interaction between maternal smoking and bed sharing on the risk of SIDS. Compared with infants not exposed to either bed sharing or maternal smoking, the adjusted OR for infants of mothers who smoked was 5.01 (95% CI = 2.01, 12.46) for bed sharing at the initial contact and 5.02 (95% CI = 1.05, 24. 05) for bed sharing at 2 months. In this study breastfeeding was not associated with a statistically significant reduction in the risk of SIDS. The other risk factors for SIDS identified were: unmarried mother, leaving school at a younger age, young mother, greater number of previous pregnancies, late attendance for antenatal care, smoking in pregnancy, male infant, Maori ethnicity, low birth weight, and shorter gestation. CONCLUSIONS: After adjustment for potential confounders, prone and side sleeping positions, maternal smoking, and the joint exposure to bed sharing and maternal smoking were associated with statistically significant increased risk of SIDS. A change from the side to the supine sleeping position could result in a substantial reduction in SIDS. Maternal smoking is common in New Zealand and with the reduction in the prevalence of prone sleeping position is now the major risk factor in this country. However, smoking behavior has been difficult to change. Bed sharing is also a major factor but appears only to be a risk to infants of mothers who smoke. Addressing bed sharing among mothers who smoke could reduce SIDS by at least one third. Breastfeeding did not appear to offer a statistically significant reduction in SIDS risk after adjustment of potential confounders, but as breastfeeding rates are comparatively good in New Zealand, this result should be interpreted with caution as the power of this study to detect a benefit is small.     

Conformation and proton configuration of pyrimidine deoxynucleoside oxidation damage products in water

Emerging data strongly suggest that the oxidation of DNA bases can contribute to genomic instability. Structural changes to DNA, induced by base oxidation, may reduce the fidelity of DNA replication and interfere with sequence-specific DNA-protein interactions. We have examined the structures of a series of pyrimidine deoxynucleoside oxidation damage products in aqueous solution. The modified nucleosides studied include the deoxynucleoside derivatives of 5-hydroxyuracil, 5-hydroxycytosine, 5-(hydroxymethyl)uracil, 5-(hydroxymethyl)cytosine, 5-formyluracil, and 5-formylcytosine. The influence of base oxidation on ionization constants, sugar conformation, and tautomeric configuration has been determined on the basis of UV, proton, and nitrogen NMR spectra of the (15)N-enriched derivatives. The potential biological consequences of the structural perturbations resulting from base oxidation are discussed.     

Foetal scalp mass spectrometer blood-gas transducer

A number of authors have described the design of transducers to be used with mass spectrometers for the skin-surface measurement of gases in newborn infants and adults. We have also previously considered the feasibility of designing a transducer for attachment to the foetal scalp during labour. This paper describes the problems which have been encountered in producing a practical transducer design for foetal scalp use. The major problem has been that of achieving adequate signal-to-noise ratio for the low oxygen levels encountered in the human foetus. A mathematical model is described, and results of the use of the model in optimising critical transducer design parameters are presented. Typical recordings obtained during labour are shown for O₂, CO₂ and N₂O.     

A simplified in vivo autoradiographic strategy for the determination of regional cerebral blood flow by positron emission tomography: theoretical considerations and validation studies in the rat

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= zeta). Integrated cranial activity CB is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that (See formula: text) where each of the terms A chi is a readily evaluated function of the blood flow rate constant kappa, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of CB vs. kappa, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBF classical X 0.99 - 0.02 (units in ml g-1 min-1; correlation coefficient r = 0.966).