Reconstitution of invariant chain function in transgenic mice in vivo by individual p31 and p41 isoforms

MHC class II molecules associate with invariant chain (li) during biosynthesis. If facilitates folding of class II molecules, interferes with their association with peptides, and is involved in their transport. The murine Ii gene encodes two chains, p31 and p41. The role of these isoforms has been studied in vitro only in inappropriate antigen-presenting cells. To circumvent this problem, we have generated invariant chain-deficient mice (delta Ii), which express exclusively the p31 and p41 isoforms. Low level expression of p31 or p41 is not sufficient for rescuing high levels of cell surface class II expression. However, low levels of the typical compact dimer conformation indicative of tight peptide binding are observed. Thus, both isoforms participate in class II folding and assembly. Furthermore, p31 and p41 retrieve the CD4+ T cell population, which is reduced in the (delta Ii) mice. Moreover, the immune response to protein antigen is restored by both isoforms.     

The effects of O- and N-linked glycosylation on the secretion and bile salt-stimulation of pancreatic carboxyl ester lipase activity

The immune status of 29 members of the Australian National Antarctic Research Expeditions (ANARE) was investigated before, during, and after a 56 day summer voyage to Antarctica and correlated with psychological and physiological parameters. All subjects were healthy. Expedition personnel demonstrated decreased cell mediated immune responses (CMI) assessed by the CMI Multi-test; 21% were hypoergic. The major associated observation was a significant negative correlation with anxiety in Antarctica. However, perceived anxiety was greater before and after the voyage. No significant changes were found in T and B lymphocyte subsets, immunoglobulin and complement components and cutaneous blood flow, nor was there any clinical evidence of illness. Of the hormones examined only cortisol was low predeparture which may reflect increased perceived anxiety at that time. Changes in immune control mechanism were apparent as shown by reduced CMI responses and lowered tetanus antibody levels. Stress factors are postulated to induce depression of the immune response in Antarctica. The association with anxiety suggests that brain peptides or associated cytokines may have a role in mediating these immune events. Such alterations in immune status have implications for health management in isolated and extreme conditions.     

Running intensity as determined by heart rate is the same in fast and slow runners in both the 10- and 21-km races

The aims of this study were to determine (1) whether running speed is directly proportional to heart rate (HR) during field testing and during 10- and 21-km races, and (2) whether running intensity, as estimated from HR measurements, differs in 10- and 21-km races and between slow and fast runners at those running distances. Male runners were divided into a fast (65-80 min for 21 km; n = 8) or slow (85-110 min for 21 km; n = 8) group. They then competed in 10- and 21-km races while wearing HR monitors. All subjects also ran in a field test in which HR was measured while they ran at predetermined speeds. The 10-km time was significantly less in the fast compared with the slow group (33:15 +/- 1:42 vs 40:07 +/- 3:01 min:s; mean +/- S.D.), as was 21-km time (74:19 +/- 4:30 vs 94:13 +/- 9:54 min:s) (P < 0.01). Despite the differences in running speed, the average running intensity (%HRmax) for the fast and slow groups in the 10-km race was 90 +/- 1 vs 89 +/- 3% and in the 21-km race 91 +/- 1 vs 89 +/- 2%, respectively. In addition, %HRmax was consistently lower in the field test at the comparative average running speeds sustained in the 10-km (P < 0.01) and 21-km (P < 0.001) races. Hence, factors in addition to work rate or running speed influence the HR response during competitive racing. This finding must be considered when running intensity for competitive events is prescribed on the basis of field testing performed under non-competitive conditions in fast and slow runners.     

Regression of left ventricular hypertrophy results in improvement of QT dispersion in patients with hypertension

OBJECTIVES: Increased QT dispersion has been considered as predisposing to ventricular arrhythmias in hypertrophic cardiomyopathy, congestive heart failure, and coronary artery disease. An increased QT dispersion has also been found in hypertensive patients with left ventricular hypertrophy (LVH). The data on the effect of LVH regression on QT dispersion are limited. METHODS AND RESULTS: To assess the relation of LVH regression and QT dispersion decrease, 68 patients (42 men and 26 women, mean age 56.3+/-9.5 years) with uncomplicated essential hypertension were studied. All underwent full electrocardiographic and echocardiographic studies at baseline and after 6 months of monotherapy, 29 with angiotensin-converting enzyme inhibitors and 39 with calcium antagonists. QT dispersion was calculated by subtracting the shortest QT from the longest QT, in absolute value (QTmax - QTmin). It was also corrected with Bazett's formula (QTc dispersion). Left ventricular mass index was assessed according to the Devereux formula. After treatment, LVH decreased with both angiotensin-converting enzyme inhibitors (from 155 to 130 g/m2, P < .001) and calcium antagonists (156 to 133/92/m2, P < .001). QT dispersion decreased both after angiotensin-converting enzyme inhibitor treatment (from 82 to 63 ms) and calcium antagonist treatment (from 77 to 63 ms, both P < .001 ). There was a significant correlation of QT dispersion and left ventricular mass after therapy (r = 0.36, P < .005). There was a correlation of the degree of LVH and QT dispersion decrease (r = 0.27, P < .05). CONCLUSIONS: It is concluded that LVH regression influences AQT favorably. Its prognostic value has yet to be determined.     

Selective astrocytic transgene expression in vitro and in vivo from the GFAP promoter in a HSV RL1 null mutant vector--potential glioblastoma targeting

Due to the lack of any effective therapy, novel approaches are currently being explored for the treatment of primary brain tumours. It has previously been demonstrated that variants of HSV-1 which are deleted in the RL1 gene and fail to produce the virulence factor ICP34.5 are potential candidates for tumour therapy. The RL1 variant 1716 replicates selectively within tumour cells and has the potential to deliver a therapeutic or tumour killing gene directly to the site of tumour growth. As many intracerebral tumours are glial and predominantly astrocytic in origin, we have evaluated the ability of 1716 to deliver a reporter gene specifically to astrocytes in vivo and in vitro using a 2.2 kb fragment which controls expression of the glial fibrillary acidic protein (GFAP), an astrocyte specific protein. Two 1716 variants, 1774 and 1775, were constructed which contain the GFAP-promoter element linked to the E. coli beta-galactosidase gene, inserted into the HSV-1 UL43 and US5 loci, respectively. In primary cultures, human primary tumour cell lines and established tumour cell lines in vitro, 1774 and 1775 gave high levels of expression of beta-galactosidase specifically in astrocytes. In vivo following intracerebral inoculation, both viruses demonstrated high levels of beta-galactosidase expression predominantly in astrocytes. These results indicate that the GFAP promoter element could be used for efficient and selective transgene delivery to human gliomas.     

Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters

The mechanisms by which inulin may elicit its lipid-lowering effect are not well elucidated. To examine the lipid-lowering potential of inulin and especially its effect on bile acid metabolism, male golden Syrian hamsters were fed semipurified diets containing 20 g/100 g fat, 0.12 g/100 g cholesterol and 0 (control), 8, 12 or 16% inulin for 5 wk. Plasma total cholesterol concentrations were significantly lowered by 18, 15 and 29% in hamsters fed 8, 12 and 16% inulin, respectively. Dietary inulin specifically decreased VLDL cholesterol, which was significantly lower in hamsters fed 16% inulin compared with controls (1.1 +/- 0.3 vs. 2.9 +/- 0.6 mmol/L). LDL and HDL cholesterol were not significantly affected by dietary inulin. Plasma triacylglycerol was significantly reduced by 40 and 63% in hamsters fed 12 and 16% inulin, respectively. Hepatic total cholesterol and particularly esterified cholesterol accumulation were significantly lower in hamsters fed 8% inulin compared with controls. All three levels of dietary inulin caused distinct alterations in the bile acid profile of gallbladder bile. Taurochenodeoxycholic acid was significantly lower, whereas glycocholic and glycodeoxycholic acid were greater in hamsters fed inulin. Daily fecal bile acid excretion (micromol/d) tended to be greater (P = 0.056) in inulin-fed hamsters compared with controls, whereas daily neutral sterol excretion was not affected. These data demonstrate that the lipid-lowering action of inulin is possibly due to several mechanisms, including altered hepatic triacylglycerol synthesis and VLDL secretion and impaired reabsorption of circulating bile acids.     

Timing and priorities for cystic fibrosis patients candidates to lung transplantation

Bilateral lung transplantation is actually considered a valuable option for patients with endstage lung disease related to cystic fibrosis. Timing is crucial to transplant successfully as many patients as possible and it is mainly based on the progressive worsening of pulmonary function tests and quality of life. We reviewed the charts of all patients accepted for lung transplantation at our institution, in order to assess the role of several functional and demographic parameters; we compared the group of patients able to successfully wait for transplantation (Group A) with patients dying on the waiting list (Group B). Twenty-eight patients were accepted: 15 were successfully transplanted (2 at other institutions) (mean waiting time: 117 days), 7 died waiting (mean waiting time: 108 days) and 6 are still on the list. We recorded FEV-1, FVC, PaO2, PaCO2, supplemental O2 requirement, 6-minute walking test, right ventricular ejection fraction (RVEF) and cardio-pulmonary hemodynamics measured at right heart catheterization; we recorded also age at time of diagnosis and at time of evaluation, sex, weight and Schwachman score. These parameters were compared between Group A and B. Age at time of evaluation, sex, weight and Schwachman score did not present any difference between the two groups, as well as pulmonary function tests, PaO2, 6-minute walk test and RVEF. A statistically significant difference was found in terms of PaCO2 (43.9 +/- 9.3 in Group A vs 69.1 +/- 32.4 in Group B, heart rate at rest (102 +/- 21 vs 131 +/- 12) mean pulmonary artery pressure (20.6 +/- 2.9 vs 36 +/- 15.7), pulmonary vascular resistances (350 +/- 96 vs 460 +/- 119.4), cardiac index (3.2 +/- 0.6 vs 5.4 +/- 0.9). On the base of our initial experience we conclude that a careful evaluation of CF candidates for lung transplantation is recommended. A deterioration of pulmonary function tests and quality of life are useful parameters to accept patients in the waiting list; however priority should be attributed also on the base of cardio-pulmonary hemodynamics. A larger series of patients is required to draw definitive conclusions.     

Teasing in hierarchical and intimate relations

Following E. Goffman's (1967) face threat analysis of social interaction, it was hypothesized that the aggressive, playful content of teasing would vary according to social status and relational satisfaction, personality, role as teaser or target, and gender. These 4 hypotheses were tested in analyses of the teasing among fraternity members (Study 1) and romantic couples (Study 2). Consistent with a face threat analysis of teasing, low-status fraternity members and satisfied romantic partners teased in more prosocial ways, defined by reduced face threat and increased redressive action. Some findings indicate that disagreeable individuals teased in less prosocial ways, consistent with studies of bullying. Targets reported more negative emotion than teasers. Although female and male romantic partners teased each other in similar ways, women found being the target of teasing more aversive, consistent with previous speculation.     

Effect of coating of aluminum carboxymethylcellulose beads on the release and bioavailability of diclofenac sodium

Menière's disease and fluctuating hearing loss are related to labyrinthine fluid pressure variations. The development of a new indirect method of analysis of the tympanic membrane displacement during the stapedial reflex, using the Marchbanks Measurements System (MMS 10), allows us to study inner ear fluid pressure during these pathological conditions. In this study, measurements with this method were made in four groups of patients: a control group with normal hearing (n=7), stable sensorineural hearing loss (n=9), fluctuating hearing loss (n=8), and Menière's disease (n=25). Results show, first, a good relationship between the recording of negative curves, suggesting a high pressure, and the acute episodes of fluctuating hearing loss; and, secondly, in the case of Menière's disease two types of situation: positive and negative curves suggesting normal and high pressures, respectively.