Whole-lung volume and density in spirometrically-gated inspiratory and expiratory CT in systemic sclerosis: correlation with static volumes at pulmonary function tests.

BACKGROUND: Spiral low-dose computed tomography (LDCT) permits to measure whole-lung volume and density in a single breath-hold. OBJECTIVE: To evaluate the agreement between static lung volumes measured with LDCT and pulmonary function test (PFT) and the correlation between the LDCT volumes and lung density in restrictive lung disease. DESIGN: Patients with Systemic Sclerosis (SSc) with (n = 24) and without (n = 16) pulmonary involvement on sequential thin-section CT and patients with chronic obstructive pulmonary disease (COPD)(n = 29) underwent spirometrically-gated LDCT at 90% and 10% of vital capacity to measure inspiratory and expiratory lung volumes and mean lung attenuation (MLA). Total lung capacity and residual volume were measured the same day of CT. RESULTS: Inspiratory [95% limits of agreement (95% LoA)--43.8% and 39.2%] and expiratory (95% LoA -45.8% and 37.1%) lung volumes measured on LDCT and PFT showed poor agreement in SSc patients with pulmonary involvement, whereas they were in substantial agreement (inspiratory 95% LoA -14.1% and 16.1%; expiratory 95% LoA -13.5% and 23%) in SSc patients without pulmonary involvement and in inspiratory scans only (95% LoA -23.1% and 20.9%) of COPD patients. Inspiratory and expiratory LDCT volumes, MLA and their deltas differentiated both SSc patients with or without pulmonary involvement from COPD patients. LDCT lung volumes and density were not correlated in SSc patients with pulmonary involvement, whereas they did correlate in SSc without pulmonary involvement and in COPD patients. CONCLUSIONS: In restrictive lung disease due to SSc there is poor agreement between static lung volumes measured using LDCT and PFT and the relationship between volume and density values on CT is altered.

Improved secretion of native human insulin-like growth factor 1 from gas1 mutant Saccharomyces cerevisiae cells.

We studied the secretion of recombinant human insulin-like growth factor 1 (rhIGF-1) from transformed yeast cells. The hIGF-1 gene was fused to the mating factor alpha prepro- leader sequence under the control of the constitutive ACT1 promoter. We found that the inactivation of the GAS1 gene in the host strain led to a supersecretory phenotype yielding a considerable increase, from 8 to 55 mg/liter, in rhIGF-1 production.

[Diffusion weighted MR: principles and clinical use in selected brain diseases]. / Studio con Risonanza Magnetica della diffusione protonica: principi e applicazioni cliniche in malattie encefaliche selezionate.

PURPOSE: To define the principles and technical bases of diffusion weighted MR imaging of the brain and report our experience in the evaluation of selected brain disorders including age-related ischemic white matter changes (leukoaraiosis), neoplastic and infective cysts and wallerian degeneration. MATERIAL AND METHODS: Between May 1999 and June 2000 we examined seventeen patients: 10 patients with leukoaraiosis and deterioration of cognitive and motor function, 5 patients with focal cystic lesions (one anaplastic astrocytoma, one glioblastoma, one metastasis from squamous cell lung carcinoma, one pyogenic abscess and one case with cerebral tubercolosis) and 2 patients with wallerian degeneration (one with post-hemorrhagic degeneration of right corticospinal tract and one with post-traumatic degeneration of left optic tract). All patients underwent a standard cranial MR examination including SE T1-, proton density, T2-weighted, FLAIR and diffusion weighted images. Post-contrast T1-weighted sequences were also obtained in the patients with cystic lesions. Diffusion weighted images were acquired with double shot echoplanar sequences. Diffusion sensitizing gradient along the x, y and z axes and b values ranging 800 to 1200 s/mm2 were used. For each slice a set of three orthogonal diffusion "anisotropic" images, an "isotropic" image and a standard T2-weighted image were reconstructed. Postprocessing included generation of the apparent diffusion coefficient maps and of the "trace" image that reflects pixel by pixel the diffusional properties of water particles only. Values of mean diffusivity within regions of interest were computed in the "trace" image and compared with those obtained in contralateral brain areas. In patients with leukoaraiosis the diffusivity in posterior periventricular white matter was compared with that measured in 10 age-matched control subjects without leukoaraiosis. RESULTS: In patients with leukoaraiosis the areas of increased periventricular signal intensity on T2-weighted images showed a significantly higher (p < 0.001) diffusivity (mean values 124.7 +/- 21.3 x 10(-5) mm2/s) as compared to control subjects (mean values 85 +/- 7 x 10(-5) mm2/s). Diffusion weighted images in 2 patients revealed the presence of a small focal area of increased signal and reduced diffusivity in "trace" images consistent with recent ischemic lesion. In neoplastic cystic lesions the central necrotic/cystic content was always hypointense on diffusion weighted images and showed increased diffusivity on "trace" images. On the other hand the central necrotic content of the pyogenic brain abscess was hyperintense and showed low diffusivity. In patients with wallerian degeneration diffusion weighted images and "trace" images demonstrated loss of anisotropy and increased diffusivity in the affected white matter tract relative to the contralateral. DISCUSSION: The increased diffusivity observed in areas of leukoaraiosis and the identification of subclinical acute ischemic lesions by diffusion weighted images might be more useful than standard MR sequences for monitoring the disease progression. Diffusion weighted images allow differentiation of the different parts of focal cystic lesions (edema, solid and cystic/necrotic portion) and are useful to differentiate pyogenic brain abscess from necrotic tumors. In patients with wallerian degeneration the loss of anisotropy and the increase of diffusivity values in the affected tract are probably related to myelin breakdown and allow better recognition of the affected tract relative to standard MR images. CONCLUSIONS: Diffusion weighted MR imaging can be performed during a standard cranial MR examination and add useful clinical information in several brain disorders besides acute ischemic stroke.

Cloning, sequencing and regulation of a cDNA encoding a small heat-shock protein from Schizosaccharomyces pombe.

We have isolated a Schizosaccharomyces pombe cDNA encoding a small heat-shock protein, designated Hsp9. The deduced amino acid sequence shares significant homology with the Saccharomyces cerevisiae Hsp12 gene product. Northern blot analysis identified a 600-base transcript which is expressed at a low level in S. pombe exponentially growing cells, but is strongly induced by heat-shock and upon entry into the stationary phase. An increase in the transcript level is also observed in response to glucose deprivation.

Candida albicans homologue of GGP1/GAS1 gene is functional in Saccharomyces cerevisiae and contains the determinants for glycosylphosphatidylinositol attachment.

The GGP1/GAS1/CWH52 gene of Saccharomyces cerevisiae encodes a major exocellular 115 kDa glycoprotein (gp115) anchored to the plasma membrane through a glycosylphosphatidylinositol (GPI). The function of gp115 is still unknown but the analysis of null mutants suggests a possible role in the control of morphogenesis. PHR1 gene isolated from Candida alibicans is homologous to the GGP1 gene. In this report we have analysed the ability of PHR1 to complement a ggp1 delta mutation in S. cerevisiae. The expression of PHR1 controlled by its natural promoter or by the GGP1 promoter has been studied. In both cases we have observed a complete complementation of the mutant phenotype. Moreover, immunological analysis has revealed that PHR1 in budding yeast gives rise to a 75-80 kDa protein anchored to the membrane through a GPI, indicating that the signal for GPI attachment present in the C. albicans gene product is functional in S. cerevisiae.