Histological appearances of the long saphenous vein

The long saphenous vein is frequently used as a graft in both coronary artery and femoro-distal bypass surgery. The histological changes which are seen after implantation into the arterial system have been well documented in the past, but little attention has been focused on the histological appearances of the donor long saphenous vein prior to grafting. In this study, samples of the long saphenous vein in excess of that required for bypass have been examined. In none of the veins did the histological appearances conform to the described normal. All showed evidence of intimal fibrosis which contained elastic tissue and enmeshed smooth muscle cells. The longitudinal and circular muscle layers showed evidence of muscle cell hypertrophy with increase in intervening connective tissue. Elsewhere, similar histological changes have been attributed to 'arterialization'. This study shows that many of the changes are present prior to grafting and may be important in graft failure.     

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.     

High level expression of recombinant mumps nucleoprotein in Saccharomyces cerevisiae and its evaluation in mumps IgM serology.

To develop improved reagents for mumps serology a high-level yeast expression system was employed to produce recombinant mumps nucleoprotein (rNP). The rNP was purified by CsCl gradient centrifugation and yielded approximately 15 mg/l of yeast culture. Electron microscopy of the rNP revealed characteristic herring-bone structures. The electrophoretic mobility of rNP in yeast cells was similar to native NP in SDS-PAGE. Monoclonal antibodies to rNP reacted with native mumps virus nucleoprotein by immunofluorescence assay. A monoclonal antibody to native mumps virus NP reacted with rNP by Western blot assay. The rNP was investigated as antigen in an IgM capture enzyme immunoassay (EIA) using a horseradish peroxidase conjugate of monoclonal antibody to the rNP. Eighteen sera previously found to be positive by IgM capture radioimmunoassay (MACRIA) and 30 sera that were mumps IgM negative by MACRIA were tested by mumps IgM capture EIA. The results for the two test were concordant. In addition, 26 rheumatoid factor positive sera and 35 sera that were IgM positive for measles, rubella or parvovirus B19 were tested. Fifty-nine sera were negative by mumps IgM capture EIA but two sera collected from two infants 3 and 6 weeks after mumps, measles and rubella vaccination were positive. Mumps MACRIA confirmed these results. Compared to MACRIA the overall sensitivity was 100% (20/20) and specificity was 96.8% (30/31). The yeast expressed rNP was highly immunogenic and suitable for use in IgM capture EIA for the diagnosis of mumps.     

The insulin sensitivity index in nondiabetic man. Correlation between clamp-derived and IVGTT-derived values

Although the minimal-model-based insulin sensitivity index (S1) can be estimated from the results of a simple 180-min intravenous glucose tolerance test (IVGTT), its relationship to widely accepted but technically more difficult clamp-based techniques has not been resolved in humans. Therefore we measured S1 by standard IVGTT, modified IVGTT, and clamp methods in 10 nondiabetic men with %IBW of 109 +/- 12 (mean +/- SD). In the euglycemic clamp studies, insulin was infused to bring insulin levels (IRI) from basal, 8 +/- 4 microU/ml, to plateaus of 21 +/- 5 and 35 +/- 6 microU/ml. S1[clamp], measured as the increase in glucose (G) clearance per increase in IRI [delta INF/(delta IRI X G)], averaged 0.29 +/- 0.09 ml/kg X min per microU/ml. In the IVGTT studies, 300 mg/kg G was given as an i.v. bolus, and G and IRI were measured for 180 min; in the modified (mod) IVGTT, tolbutamide (300-500 mg) was given i.v. 20 min after the G to observe the effect of an IRI peak on G removal after G level was free of initial "mixing" effects. The S1 estimated by computer did not differ significantly between standard [(6.9 +/- 3.4) X 10(-4) min-1 per microU/ml] and modified [(6.7 +/- 3.5) X 10(-4) min-1 per microU/ml] tests, indicating no bias due to the differing insulin patterns and levels. There was a strong positive correlation between S1 (mod IVGTT) and S1(clamp): r = 0.84; N = 10; P less than 0.002. The correlation between S1(standard IVGTT) and S1(clamp) was 0.54, suggesting the modified test is less "noisy." Nonetheless, in eight euglycemic women with a wider range of adiposity, S1(standard IVGTT) has been significantly correlated with %IBW (r = -0.72) and basal IRI (r = -0.84). The correlation between S1 measures by clamp and IVGTT methods provides one step toward validation of the minimal model for studies of insulin action in man.     

Tumour necrosis factor beta (lymphotoxin) inhibits locomotion and stimulates the respiratory burst and degranulation of neutrophils.

The data presented here demonstrate that recombinant human tumour necrosis factor beta (rHuTNF beta; lymphotoxin) is a neutrophil modulator. The lymphokine inhibited the locomotion of neutrophils and augmented the neutrophil oxygen-dependent respiratory burst in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and phorbol myristate acetate (PMA), as measured by their capacity to produce chemiluminescence, H2O2 and superoxide. The effects on the respiratory burst occurred at a tenth of the concentration of TNF beta required to inhibit locomotion. After incubation with TNF beta, the neutrophils could be washed without any reduction in their capacity to show augmented responses. The TNF beta enhanced granule enzyme (lysozyme and beta-glucuronidase) release of neutrophils stimulated with cytochalasin B-FMLP.     

A population-based study of the relationship between salt intake, bone resorption and bone mass

OBJECTIVE: To explore the relationship between urinary sodium (the best measure of salt intake), urinary calcium, urinary deoxypyridinoline (DPYR) and bone mass. DESIGN: Cross-sectional study. SETTING: Population based sample of healthy Hobart residents. SUBJECTS: One hundred and fifty-four (M = 34, F = 120) subjects invited to take part from a systematic sample of the electoral roll and a single newspaper advertisement. RESULTS: In both sexes, urinary sodium correlated moderately with urinary DPYR (r = 0.32, P < 0.0001) and urinary calcium (r = 0.37, P < 0.0001). In multivariate analysis, the combination of urinary sodium, total body bone area, age and sex explained 22% of the variation in log-transformed DPYR (P < 0.00001). In univariate analysis, both urinary sodium and urinary DPYR were strongly associated with bone mineral content and bone mineral density at all sites but this association disappeared after adjustment for confounders particularly body weight. CONCLUSIONS: This study has shown that salt intake is associated with markers of bone resorption in a population-based sample of males and females and appears likely to be a risk factor for osteoporosis despite the lack of a demonstrable association between bone mass and a single measure of urinary sodium excretion. Further studies are needed to define the effect of salt intake on bone mass and fractures more clearly. These studies will need to be either longitudinal or interventional in design with repeated measures of urinary sodium so that habitual sodium intake can be accurately assessed and regression dilution bias can be minimised.     

PTSD and Comorbid Psychotic Disorder: Comparison with Veterans Diagnosed with PTSD or Psychotic Disorder

Symptoms of posttraumatic stress disorder (PTSD), psychosis, general psychopathology, role functioning, violence potential, and cognitive and emotional aspects of psychotic states were compared in three groups of veterans. Groups were defined on the basis of their DSM-IV diagnoses: Psychotic disorder and war-related PTSD, war-related PTSD without psychotic symptoms, and psychotic disorder without PTSD. Veterans with PTSD and a comorbid psychotic disorder showed significantly higher levels of positive symptoms of psychosis, general psychopathology, paranoia, and violent thoughts, feelings, and behaviors than the other two groups. These data show that patients with comorbid PTSD and psychotic disorder show levels of cognitive, emotional, and behavioral disturbance that far exceed the levels of disturbance seen in patients with PTSD without psychosis or in patients with psychotic disorder.     

Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brain

Hypotransferrinemia (hpx/hpx) is a genetic defect in mice resulting in <1% of normal plasma transferrin (Tf) concentrations; heterozygotes for this mutation (+/hpx) have low circulating Tf concentrations. These mice provide a unique opportunity to examine the role of Tf in Fe and Mn transport in the brain. Twenty weanling wild-type BALB/cJ mice, 15 +/hpx mice, and 12 hpx/hpx mice of both sexes were injected i.v. with either 54MnCl(2) or 59FeCl(3) either 1 h or 1 week before killing at 12 weeks of age. Total brain counts of 54Mn and 59Fe were measured, and regional brain distributions were assessed by autoradiography. Hypotransferrinemia did not affect total brain Mn uptake. However, 1 week after i.v. injection, hpx/hpx mice had less 54Mn in forebrain structures including cerebral cortex, corpus callosum, striatum, and substantia nigra. The +/hpx mice had the highest total brain 59Fe accumulation 1 h after i.v. injection. A striking effect of regional distribution of 59Fe was noted 1 week after injection; in hpx/hpx mice, 59Fe was located primarily in choroid plexus, whereas in +/+ and +/hpx mice 59Fe was widely distributed, with relatively high amounts in cerebral cortex and cerebellum. We interpret these data to mean that Tf is necessary for the transport of Fe but not Mn across the blood-brain barrier, and that there is a Tf-independent uptake mechanism for iron in the choroid plexus. Additionally, these data suggest that endogenous synthesis of Tf is necessary for Fe transport from the choroid plexus.     

The role of simple non-invasive testing in infra-inguinal vein graft surveillance

A prospective vein graft screening programme was established in order to improve graft patency in the period 1-12 months after operation. Patient assessment consisted of ankle:brachial pressure index (ABPI) measurement before and after exercise, and Duplex scanning. Thirty-nine grafts have been followed up, with 19 stenoses detected in 18 grafts (46%) using Duplex. Of these 18 grafts, six had a serial fall in resting ABPI, median 0.14 (range 0.11-0.33), and nine had a post-exercise ABPI fall, median 0.19 (range 0.13-0.4). The remaining three had a normal ABPI but were unable to exercise. Fifteen grafts have been treated, 12 by percutaneous transluminal angioplasty (PTA), and three by surgery. One stenosis treated with PTA recurred within 3 months and was repaired with a vein patch. Since screening was implemented no grafts in the programme have occluded. This study indicates that simple ABPI measurements can be used to screen "at risk" grafts for evaluation with Duplex scanning, without jeopardising graft patency.