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41.
In Situ Detection of Apoptosis at Sites of Chronic Bacterially Induced Inflammation in Human Gingiva
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Apoptosis is a key phenomenon in the regulation of the life span of terminally differentiated leukocytes. Human gingiva represents an established model to study immune responses to bacterial infection. In this investigation, we used the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) technique to evaluate presence and topographic location of apoptosis-associated DNA damage in human gingival biopsies along with the expression of the p53 and Bcl-2 apoptosis-regulating proteins. Qualitative data analysis showed high densities of cells expressing DNA damage and p53 both within the epithelial attachment to the tooth and in the perivascular infiltrate (infiltrated connective tissue [ICT]) immediately underlying the site of chronic bacterial aggression. Topographic consistency between DNA damage- and p53-positive cells was consistently observed. Quantitative analysis of the ICT showed mean densities of DNA damage- and p53-positive cells of 345 ± 278 and 403 ± 182 cells/mm2, respectively. Numerical consistency was confirmed by multivariate regression analysis: densities of DNA damage-positive cells were significantly predicted by densities of p53-positive cells (P = 0.001, r2 = 0.84). In the ICT, cells displaying biotinylated DNA nicks were 3.8% ± 2.7% of total cellularity, while p53- and Bcl-2-positive cells represented 4.4% ± 1.7% and 15.4% ± 6.7% of total cells, respectively. It is suggested that p53 expression associated with DNA damage is a prevalent phenomenon in chronically inflamed human gingiva, and that apoptosis may be a relevant process for the maintenance of local immune homeostasis at sites of chronic bacterial challenge in vivo. 相似文献
42.
B. Grassi P. Mognoni M. Marzorati S. Mattiotti C. Marconi P. Cerretelli 《Acta physiologica (Oxford, England)》2001,172(3):189-194
Anecdotal observations suggest that the reduction in peak lactate accumulation in blood ([La]b peak) after exhausting exercise, in chronic hypoxia vs. normoxia, may be related to the duration of the exercise protocol, being less pronounced after short supramaximal exercise than after incremental exercise (IE) lasting several minutes. To test this hypothesis, six healthy male Caucasians (age 36.8 ± 7.3, x¯ ± SD) underwent three exercise protocols on a cycle ergometer, at sea level (SL) and after 21 ± 10 days at 5050 m altitude (ALT): (1) 10 s, (2) 30 s ‘all out’ exercise and (3) IE leading to exhaustion in ~20–25 min. ‘Average’ power output (p¯) was calculated for 10 or 30 s ‘all out’; maximal power output (Pmax) was determined for IE. Lactate concentration in arterialized capillary blood ([La]b) was measured at rest and at different times during recovery; the highest [La]b during recovery was taken as [La]b peak. No significant differences in p¯ were observed between SL and ALT, for either 10 or 30 s ‘all out’ exercise; Pmax during IE was significantly lower at ALT than at SL. [La]b peak after 10 s ‘all out’ was unaffected by chronic hypoxia (7.0 ± 0.9 at ALT vs. 6.3 ± 1.8 mmol L–1 at SL). After 30 s ‘all out’ the [La]b peak decrease, at ALT (10.6 ± 0.6 mmol L–1) vs. SL (12.9 ± 1.4 mmol L–1), was only ~50% of that observed for IE (6.7 ± 1.6 mmol L–1 vs. 11.3 ± 2.8 mmol L–1). Muscle power output and blood lactate accumulation during short supramaximal exercise are substantially unaffected by chronic hypoxia. 相似文献
43.
Arciola CR Campoccia D Gamberini S Donati ME Pirini V Visai L Speziale P Montanaro L 《Biomaterials》2005,26(33):6530-6535
The opportunistic pathogen Staphylococcus epidermidis is able to produce biofilm and to frequently cause implant infections. In recent years, it has also exhibited an increasing antimicrobial drug resistance. Here, the resistance to a panel of 16 different antibiotics in 342 clinical strains of S. epidermidis from orthopaedic implant infections has been investigated. The isolates were pheno- and genotyped for extracellular polysaccharide production, relevant to staphylococcal biofilm formation, in order to ascertain possible associations with antibiotic resistance. Approximately 10% of the isolates were found to be sensitive to all screened antibiotics. In all, 37-38% were resistant to beta-lactams such as oxacillin and imipenem, while the resistance to penicillin, ampicillin, cefazolin, cefamandole, was consistently observed in over 80% of the strains. Erythromycin- and clindamycin- resistant strains were approximately 41% and 16%, respectively. Of the isolates, 10% was resistant to chloramphenicol, 23% to sulfamethoxazole and 26% to ciprofloxacin. Resistance to vancomycin was never observed. Interestingly, exopolysaccharide-producing strains exhibited a significantly higher prevalence in the resistance to the four aminoglycosides (gentamicin, amikacin, netilmicin, tobramycin), to sulfamethoxazole and to ciprofloxacin with respect to non-producing isolates. Moreover, multiple resistance to antibiotics was more frequent among exopolysaccharide-forming strains. 相似文献
44.
Marianna Farnè Giovanna M. Tedesco Chiara Bedetti Amedea Mencarelli Daniela Rogaia Davide Colavito Giuseppe Di Cara Gabriela Stangoni Stefania Troiani Alessandra Ferlini Paolo Prontera 《American journal of medical genetics. Part A》2020,182(10):2377-2383
Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth. 相似文献
45.
Zauli D Contestabile S Grassi A Bortolotti R Ballardini G Bianchi FB 《The Journal of allergy and clinical immunology》2002,110(3):538-9; author reply 539
46.
A case of primary low grade B cell lymphoma of the salivary gland associated with a low grade B cell lymphoma of the thymus and involvement of the skin is reported. The lesions in the salivary gland and in the thymus showed the typical features of a lymphoma arising from the mucosa associated lymphoid tissue (MALT) and comprised lymphatic follicles, centrocyte-like (CCL) cells and lymphoepithelial lesions. Immunohistochemistry and Southern blot analysis supported the hypothesis that these lesions can originate from the same cellular clone. These findings confirm the occurrence of low grade B cell MALT lymphoma in the thymus and the possibility of spread of MALT lymphoma to other mucosal sites. 相似文献
47.
Paolo Cerretelli Bruno Grassi Lei Xi Federico Schena Claudio Marconi Michael Meyer Guido Ferretti 《European journal of applied physiology》1995,71(4):287-294
To gain an insight into the origin of the phase I ventilatory response to exercise (ph I) in humans, pulmonary ventilation WE) and end-tidal partial pressures of oxygen and carbon dioxide (P
ETO2 and P
ETCO2, respectively) were measured breath-by-breath in six male subjects during constant-intensity exercise on the cycle ergometer at 50, 100 and 150 W, with eupnoeic normocapnia (N) or hyperpnoeic hypocapnia (H) established prior to the exercise test. Cardiac output (Q2) was also determined beat-by-beat by impedance cardiography on eight subjects during moderate exercise (50 W), and the C02 flow to the lungs (Q2·CvCO2 where CvCO2 is concentration of CO2 in mixed veneous blood) was estimated with a time resolution of one breathing cycle. In N, the initial abrupt increase of PE during ph I (VE approximately 18 l · min–1 above rest) was followed by a transient fall. When P
ETCO2 started to increase (and P
ETO2 decreased) VE increased again (phase II ventilatory response, ph II). In H, during ph I VE was similar to that of N. By contrast, during ph II VE kept gradually decreasing and started to increase only when P
ETCO2 had returned to approximately 40 mmHg (5.3 kPa). Thus, as a result of the prevailing initial conditions (N or H) a temporal shift of the time-course of VE during ph II became apparent. No correlation was found between C02 flow to the lungs and VE during ph I. These results are interpreted as suggesting that an increased C02 flow to the lungs does not constitute an important factor for the initial hyperventilatory response to exercise. They are rather compatible with a neural origin of ph I, and would support the neurohumoral theory of ventilatory control during exercise. 相似文献
48.
Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients. 总被引:2,自引:0,他引:2
Davide Treré Claudio Ceccarelli Mario Migaldi Donatella Santini Mario Taffurelli Elena Tosti Pasquale Chieco Massimo Derenzini 《Applied immunohistochemistry & molecular morphology》2006,14(3):314-323
The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments. 相似文献
49.
Influence of visual experience on developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei 总被引:1,自引:0,他引:1
Silvarosa Grassi Cristina Dieni Adele Frondaroli Vito Enrico Pettorossi 《The Journal of physiology》2004,560(3):767-777
The influence of visual experience deprivation on changes in synaptic plasticity during postnatal development was studied in the ventral part of the rat medial vestibular nuclei (vMVN). We analysed the differences in the occurrence, expressed as a percentage, of long-term depression (LTD) and long-term potentiation (LTP) induced by high frequency stimulation (HFS) of the primary vestibular afferents in rats reared in the light (LR) and those in the dark (DR). In LR rats, HFS only induced LTD in the early stages of development, but the occurrence of LTD progressively decreased to zero before their eyes opened, while that of LTP enhanced from zero to about 50%. Once the rats' eyes had opened, LTD was no longer inducible while LTP occurrence gradually reached the normal adult value (70%). In DR rats, a similar shift from LTD to LTP was observed before their eyes opened, showing only a slightly slower LTD decay and LTP growth, and the LTD annulment was delayed by 1 day. By contrast, the time courses of LTD and LTP development in DR and LR rats showed remarkable differences following eye opening. In fact, LTD occurrence increased to about 50% in a short period of time and remained high until the adult stage. In addition, the occurrence of LTP slowly decreased to less than 20%. The effect of light-deprivation was reversible, since the exposure of DR rats to light, 5 days after eye opening, caused a sudden disappearance of LTD and a partial recover of LTP occurrence. In addition, we observed that a week of light deprivation in LR adult rats did not affect the normal adult LTP occurrence. These results provide evidence that in a critical period of development visual input plays a crucial role in shaping synaptic plasticity of the vMVN, and suggest that the visual guided shift from LTD to LTP during development may be necessary to refine and consolidate vestibular circuitry. 相似文献
50.
Effects of nitric oxide synthase inhibition by l-NAME on oxygen uptake kinetics in isolated canine muscle in situ 总被引:2,自引:2,他引:2
Bruno Grassi Michael C. Hogan Kevin M. Kelley Richard A. Howlett L. Bruce Gladden 《The Journal of physiology》2005,568(3):1021-1033
We hypothesized that an acute bout of strenuous, non-damaging exercise would increase rates of protein synthesis of collagen in tendon and skeletal muscle but these would be less than those of muscle myofibrillar and sarcoplasmic proteins. Two groups ( n = 8 and 6) of healthy young men were studied over 72 h after 1 h of one-legged kicking exercise at 67% of maximum workload ( W max ). To label tissue proteins in muscle and tendon primed, constant infusions of [1-13 C]leucine or [1-13 C]valine and flooding doses of [15 N] or [13 C]proline were given intravenously, with estimation of labelling in target proteins by gas chromatography–mass spectrometry. Patellar tendon and quadriceps biopsies were taken in exercised and rested legs at 6, 24, 42 or 48 and 72 h after exercise. The fractional synthetic rates of all proteins were elevated at 6 h and rose rapidly to peak at 24 h post exercise (tendon collagen (0.077% h−1 ), muscle collagen (0.054% h−1 ), myofibrillar protein (0.121% h−1 ), and sarcoplasmic protein (0.134% h−1 )). The rates decreased toward basal values by 72 h although rates of tendon collagen and myofibrillar protein synthesis remained elevated. There was no tissue damage of muscle visible on histological evaluation. Neither tissue microdialysate nor serum concentrations of IGF-I and IGF binding proteins (IGFBP-3 and IGFBP-4) or procollagen type I N-terminal propeptide changed from resting values. Thus, there is a rapid increase in collagen synthesis after strenuous exercise in human tendon and muscle. The similar time course of changes of protein synthetic rates in different cell types supports the idea of coordinated musculotendinous adaptation. 相似文献