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Biomedical subjects

S Milani

Publications and source records attributed to S Milani.

At least 91 records · Page 5Linked to original sources
PubMed1993

Regulation of extracellular matrix synthesis by transforming growth factor beta 1 in human fat-storing cells.

BACKGROUND: Fat storing cells (FSC) are nonparenchymal liver cells generally considered the major source of the hepatic extracellular matrix (ECM). Transforming growth factor beta 1 (TGF-beta 1) is a potent regulator of ECM synthesis in various cell types. In this study, the effect of TGF-beta 1 on procollagen types I, III, IV, laminin (Lam), and fibronectin (FN) synthesis in cultured human FSCs was analyzed. METHODS: FSCs were isolated from wedge sections of normal human livers. Morphological studies were performed by immunofluorescence and electron microscopy. ECM components in human FSC cultures were measured by an enzyme-linked immunosorbent assay. The expression of messenger RNA (mRNA) was evaluated by Northern blot and in situ hybridization. RESULTS: Cultured human FSCs displayed numerous fat droplets in the perinuclear zone, and immunoreactivity for vimentin and alpha-smooth muscle actin. A weak nonfibrillar staining was observed by using a polyclonal antidesmin antibody. TGF-beta 1 induced a dose-dependent increase of procollagen I, III, and FN accumulation in human FSC cultures, whereas procollagen IV and Lam production was not affected. Furthermore, TGF-beta 1 increased the expression of alpha 1 (I), alpha 1 (III) procollagen, FN and TGF-beta 1 mRNA in human FSC cultures. CONCLUSIONS: These data indicate that TGF-beta 1 is able to increase the synthesis of procollagen I, III, and FN in cultured human FSCs. Moreover, TGF-beta 1 can induce its own mRNA in the same cells.

Adipose Tissue↗
PubMed1993

Differential effects of dopamine D-1 and D-2 receptor antagonist antipsychotics on sleep-wake patterns in the rat.

A series of antipsychotics having different selectivity for dopamine (DA) D-1 and D-2 receptors were studied for their effects on sleep stages in the rat. Electroencephalographic activity was recorded and classified according to the stages of wakefulness, rapid eye movement (REM) sleep and non-REM sleep. Total sleep duration, non-REM and REM latencies, number and duration of REM episodes were calculated. The DA D-1 antagonists, SCH 23390 (0.001-0.1 mg/kg s.c.), SCH 39166 (0.01-0.3 mg/kg s.c.) and NNC-756 (0.003-0.1 mg/kg s.c.), enhanced markedly the time spent in sleep through a significant increase of both non-REM and REM. Enhancement of REM was due to an increase in the number of episodes. The selective DA D-2 antagonists, raclopride (0.03-1 mg/kg s.c.) and remoxipride (1-10 mg/kg s.c.), did not affect sleep stages. Haloperidol (0.1-3 mg/kg p.o.) increased the duration of total sleep through an increase of non-REM, leaving REM unmodified. The nonselective DA antagonists, chlorpromazine (0.3-3 mg/kg s.c.) and clozapine (0.3-3 mg/kg s.c.) produced either no effect or slightly increased non-REM, respectively. Both drugs reduced REM duration by lowering the number and duration of episodes. The data show that there are differences between DA D-1 and D-2 antagonists with regard to their effects on sleep and wakefulness. Concomitant enhancement of both total sleep and REM appears to be a peculiar feature which clearly distinguishes DA D-1 antagonists from the other DA receptor blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cellular localization of procollagen gene transcripts in inflammatory bowel diseases.

The cellular localization of procollagen types I, III, IV, and V gene transcripts was determined in tissues from 12 patients with either Crohn's disease (CD) or ulcerative colitis (UC) and nine controls by in situ hybridization with 35S-labeled RNA probes. In CD, the signal intensity and number of labeled cells were significantly increased, particularly in deeper intestinal layers. In contrast, the labeled cells in UC were concentrated in the subepithelial intestinal layers, with an overexpression of procollagen III RNA transcripts. Immunohistological stainings for procollagen types I, III, and IV showed a weaker staining in UC than in CD, indicating that increased transcript levels in UC are unrelated to the enhanced collagen protein deposition, although the increase of procollagen messenger RNA levels correlated with the density of the inflammatory infiltrate. It was concluded that both CD and UC show highly increased procollagen RNA transcript levels but differ in collagen deposition. Thus, different posttranscriptional or posttranslational regulatory mechanisms, such as collagen degradation, may account for the observed differences.

Adult↗
PubMed1992

Effects of sulglycotide on endogenous prostaglandin synthesis in human antral mucosa.

The effect of sulglycotide, a polysulphated glycopeptide isolated from pig duodenum, on PGE2, 6-ketoPGF1 alpha and TxB2 production from isolated biopsy specimens of human antral mucosa was investigated in vitro, in comparison with carbenoxolone. In addition to a tendency toward increased PGE2 production just short of statistical significance, both sulglycotide and carbenoxolone significantly increased 6-ketoPGF1 alpha accumulation in the incubation medium. TxB2 levels were not significantly modified by the two drugs. Therefore, changes in the prostanoid production by human antral mucosa could, at least partially account for the cytoprotective effects of sulglycotide in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients.

Liver perisinusoidal fat-storing cells (FSC) show morphological and ultrastructural characteristics similar to pericytes regulating local blood flow in other organs. In the present study we have analyzed whether FSC respond to local vasoconstrictors such as thrombin, angiotensin-II, and endothelin-1 with an increase in intracellular free calcium concentration ([Ca2+]i) coupled with effective cell contraction. All agonists tested induced a rapid and dose-dependent increase in [Ca2+]i followed by a sustained phase lasting several minutes in confluent monolayers of Fura-2-loaded human FSC. Pharmacological studies performed using different Ca2+ channel blockers indicated that, at least for thrombin and angiotensin-II, the sustained phase is due to the opening of voltage-sensitive membrane Ca2+ channels. To analyze the temporal and spatial dynamics of Ca2+ release in response to these agonists, we performed experiments on individual Fura-2-loaded human FSC using a dual wavelength, radiometric video imaging system. The rise in [Ca2+]i was exclusively localized to the cytoplasm, particularly in the branching processes. Increases in [Ca2+]i more than four-fold were associated with a simultaneous and transient reduction of cell area indicating reversible cell contraction. Our results indicate that the Ca(2+)-dependent contraction of human FSC in vitro may reflect a potential role in regulating sinusoidal blood flow in vivo.

Angiotensin II↗
PubMed1992

[Pathomorphology of acute and chronic stages of CCl4-induced liver fibrosis: immunohistochemical and in situ hybridization studies].

The cellular localization of expression of various genes activated during the course of liver fibrosis and regeneration was studied by immunohistology and in situ hybridization in rat and human liver tissues. Mesenchymal cells proved to be the principal sources of extracellular matrix proteins and of fibrogenic growth factors, whereas the collagenase-activating protease transin/stromelysin gene was transcribed in parenchymal cells as well. Fibrogenesis by the mesenchymal compartment appears to be balanced by fibrolysis controlled by parenchymal cell functions. Continuous parenchymal damage may thus disrupt this balance between fibrogenesis and fibrolysis, resulting in fibrosis.

Animals↗
PubMed1991

Comparison of growth retarding effects induced by two different glucocorticoids in prepubertal sick children: an interim long-term analysis.

The low interference with growth expected in child for a cortisol analogue, deflazacort (DFZ), prompted us to verify if DFZ could affect growth less than prednisone (PDN). An interim analysis relative to 27 girls and 38 boys (out of 100 expected) aged 3-12 yrs, after a median period of 14 mo.s is reported. Children with connective tissues (CTD) and glomerular disorders (KD) were randomly allocated to DFZ or PDN. Anthropometric measurements and maturity ratings were performed. Mean daily doses of PDN (or DFZ equivalent), from 0.57 to 0.64 mg/kg (DFZ 0.92 to 0.94 mg/kg) to induce control and from 0.19 to 0.39 mg/kg (DFZ 0.34 to 0.36 mg/kg) to maintain disease under control were given in CTD and KD, respectively. The increase in bone age delay over time was significantly greater than for PDN (-4.0 mo/yr) than DFZ (-1.8 mo/yr) in the overall group. The increases in statural age delay and loss over time were significantly greater than for PDN (-5.9 and -5.9 mo/yr) than DFZ (-2.4 and -2.4 mo/yr), only in children with "taller" midparents. Although doses of DFZ 1.1-1.8 times those of PDN were given, growth retardation in PDN-treated children was nevertheless 2.3-2.5 times that in DFZ-ones.

Age Determination by Skeleton↗
PubMed1991

Temporal and spatial patterns of transin/stromelysin RNA expression following toxic injury in rat liver.

We have examined the expression of the extracellular matrix-degrading metalloprotease transin/stromelysin during the early phases of rat liver regeneration following toxic injury by a single dose of carbon tetrachloride (CCl4). In situ hybridization displayed cell type-specific spatial and temporal RNA expression patterns with high transcript levels in small proportions of hepatocytes and non-parenchymal cells, peaking at 24 and 48 h after intoxication, respectively. In agreement with the presence of c-fos and c-jun recognition sites on the transin gene, expression of these oncogenes preceded transin expression. Transin-expressing hepatocytes were largely localized in areas subsequently eliminated by necrosis due to CCl4 intoxication. As a consequence of these expression patterns and the key function of transin as an activator of interstitial collagenase, it seems that the hepatic fibrosis observed after CCl4 administration may be related to fibrogenesis unbalanced by fibrolysis due to altered transin expression.

Animals↗
PubMed1991

Effects of selected beta-adrenergic blocking agents on sleep stages in spontaneously hypertensive rats.

The effects on sleep of six beta-adrenergic blockers (propranolol, dilevalol, pindolol, metoprolol, celiprolol and atenolol) which differ in their pharmacological characteristics were studied in spontaneously hypertensive rats. Electroencephalographic activity was recorded for 6 hr after p.o. administration of drugs or vehicle, and the stages of wakefulness, rapid eye movements (REM) sleep and non-REM sleep (non-REM) were classified thereafter. In separate experiments antihypertensive activity of each drug was assessed by the tail-cuff technique. The most common effect of the beta-blockers examined was a decrease of the duration of REM. The effect was marked for propranolol (10-100 mg/kg), celiprolol (10-100 mg/kg) and pindolol (1-10 mg/kg), whereas it occurred at low doses, but not at high doses for metoprolol (10 mg/kg) and atenolol (3 and 10 mg/kg). Dilevalol induced a moderate REM decrease at 30 mg/kg only. For the beta-1 antagonists, the dose reducing REM substantially (ED30) was slightly above (1.4- to 3.7-fold) that effective on blood pressure (ED10), whereas the separation was high for pindolol (17.4-fold) and dilevalol (22.4-fold). Conversely, propranolol displayed a weak antihypertensive activity in this model and was more potent on REM than in reducing blood pressure. Propranolol, celiprolol and atenolol also increased duration of wakefulness. Considering the pharmacological characteristics of the beta-blockers examined, it is suggested that selective beta-1 antagonism and interaction with other neurotransmitters, such as serotonin, are relevant to the potential effects of this class of antihypertensive drugs on sleep function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease.

Transforming growth factor (TGF) beta 1 has been implicated in the control of hepatocyte growth and stimulation of extracellular matrix synthesis in acute and chronic liver disease. The cellular localization of transforming growth factor (TGF) beta 1 and beta 2 RNA transcripts was determined in normal and fibrotic liver by in situ hybridization with [35S]-labeled RNA probes in combination with immunostaining for cell type characteristic markers. Fibrotic specimens were from patients with hepatitis B virus infection or alcohol abuse and rats with fibrosis secondary to bile duct ligation and scission. In normal liver, low levels of TGF beta 1 transcripts were found in some portal tract stromal cells, and TGF beta 2 RNA was not detectable. In fibrotic liver, high TGF beta 1 RNA levels were present in most mesenchymal liver cells, in most inflammatory cells, and in few bile duct epithelial cells. Hepatocytes did not express this cytokine with the exception of few limiting plate hepatocytes in cases of human cirrhosis with high activity. TGF beta 2 transcripts were detected at high levels in proliferating bile ducts of fibrotic livers, but were absent in all other cell types. TGF beta 1 expression in the liver is thus a function predominantly of mononuclear and mesenchymal cells as well as of some hepatocytes, whereas TGF beta 2 expression is a specific property of bile duct epithelial cells that may be related to the formation of specialized periductular connective tissue during bile duct proliferation.

Animals↗
PubMed1991

Duodenal ulcer and Sjogren's syndrome in patients with primary biliary cirrhosis: a casual association?

Peptic ulcer has been reported in patients with primary biliary cirrhosis (PBC), but its frequency and pathogenesis are still poorly defined. We have analyzed the occurrence of duodenal ulcer in 37 female patients affected by PBC and in 35 with chronic liver disease of various etiologies. An active ulcer was found in seven patients with PBC and in one with chronic autoimmune hepatitis. The presence of an exocrine gland defect, as indicated by clinical signs of Sjogren's syndrome (SS), was found in six patients with PBC and duodenal ulcer (85%), but in only eight (26.6%) of those without ulcer (p less than 0.02). Therefore, in our patients, duodenal ulcer occurs more often in PBC than in other types of chronic liver disease. The association of SS with PBC, significantly higher in patients with than without ulcer, supports the hypothesis that the underlying exocrine gland defect is involved in the development of duodenal ulcer.

Adult↗
PubMed1991

Temporal and spatial patterns of proto-oncogene expression at early stages of toxic liver injury in the rat.

Sequential and transient expression of c-fos, c-jun, c-myc, c-Ha-ras and c-Ki-ras proto-oncogene RNA transcripts with zonal heterogeneity was demonstrated in virtually all hepatocytes of adult rat liver by in situ hybridization with single-stranded, [35S]-labeled cRNA probes at various time points after intraperitoneal administration of a single dose of carbon tetrachloride (CCl4). After a brief interval, elevated RNA levels of these genes were also observed in nonparenchymal cells. A second phase of proto-oncogene expression was characterized by high RNA levels in only a fraction of parenchymal cells with preference of mediolobular areas. Distribution and number of these cells were comparable tl hepatocytes expressing the proliferation-associated nuclear antigen Ki-67 72 hours after toxic injury. Oncogene expression in the nonparenchymal compartment correlated with distinct morphologic changes preceding type I procollagen gene expression by desmin-positive perisinusoidal cells, accumulating together with numerous c-fms expressing cells in the areas of hepatocellular necrosis. We conclude that zonal hepatic destruction by carbon tetrachloride induces proto-oncogene expression with distinct temporal and spatial patterns initiated by the most severely damaged hepatocytes. Proto-oncogene products thus represent valuable markers of cellular activation preceding and accompanying various aspects of tissue repair reactions.

Animals↗
PubMed1990

Observer variation in mammary thermography: results of a teaching file test carried out in four different centers.

To evaluate observer variation in mammary thermography, a teaching file test of 159 thermographies was worked out by 4 senology centers. The evaluation of accuracy and the K index of variability demonstrated a significant variability among centers. The reliability of thermography in senology seems to be too poor for it to be able to direct any therapeutic decision, either diagnostic or prognostic.

Breast Neoplasms↗
PubMed1990

Modified Greulich-Pyle, Tanner-Whitehouse, and Roche-Wainer-Thissen (knee) methods for skeletal age assessment in a group of Italian children and adolescents.

Modified Greulich-Pyle (GP), Tanner et al. 2, radius, ulna and short bones (TW2-RUS), TW2-20-bone and Roche-Wainer-Thissen RWT (knee) skeletal age assessments were made in an Italian population sample of 128 males and 93 females aged 4.1-16.9 years. All the scales appear to be well-suited to the Italian population despite minor differences. A very high correlation was found between the assessment of knee skeletal ages by the RWT method and that of the hand-wrist by the GP and TW2 systems in the same subject without sex and age-associated variations.

Adolescent↗
PubMed1990

Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis.

To localize the cellular sources of the collagens excessively deposited in the liver in the course of secondary biliary fibrosis, we have analyzed by in situ hybridization the distribution of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen and albumin RNA transcripts in rat livers up to 6 wk following common bile duct ligation and scission. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen RNA were found in nonparenchymal cells, while alpha 1(IV) procollagen gene expression was at the threshold of detection. Following bile duct obstruction, increasing amounts of alpha 2(I), alpha 1(III), and alpha 1(IV) procollagen gene transcripts were observed in cells of the expanding portal tracts and in perisinusoidal cells in areas of excessive collagen deposition. Procollagen gene expressing perisinusoidal cells were colocalized with desmin-immunoreactive cells, suggesting that Ito cells and transitional cells were among the collagen-expressing cell types. Only alpha 1(IV) procollagen transcripts were found in epithelial cells of newly formed bile ducts. Neither normal nor fibrotic liver showed any hybridization signal above background over hepatocytes, indicating that hepatocytes are unlikely to be a major source of hepatic collagen.

Animals↗
PubMed1990

Technical variability of bone histomorphometric measurements.

Effects of main sources of bone biopsy sample variability have been examined. Variability was assessed in double iliac crest biopsies of 12 subjects with normal or pathological bone. Components of variance were estimated as follows: two biopsies per patient; three specimens at different distances from compact bone; three sections per specimen; three microscopic fields per section. The following indicators were measured: bone volume (BV/TV); osteoid volume (OV/BV); osteoid surface (OS/BS); osteoblast surface (Ob.S/BS); eroded surface (ES/BS); osteoclast surface (Oc.S/BS); osteoid thickness (O.Th). Sources of variability were assessed by ANOVA for random effects. On the basis of the results, between fields variation gave the main contribution to the error of single measures (BV/TV, 50%; O.Th, 70%; OV/BV, Ob.S/BS, OS/BS, Oc.S/BS, ES/BS more than 80%). Distance from compact bone affected mostly the BV/TV (40%) and the O.Th (10%) error. When bone specimens at intermediate distance from cortical bone are examined, variations due to different biopsies, different section and different microscopic field are largely reduced by measuring 12 microscopic fields for BV/TV (14%) and 48 microscopic fields for the other indicators (O.Th 16%; OV/BV, Ob.S/BS, OS/BS, Oc.S/BS, ES/BS more than 30%). The precision can be only slightly improved by further increasing the number of the microscopic fields.

Biopsy↗