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Biomedical subjects

L Caputo

Publications and source records attributed to L Caputo.

At least 19 recordsLinked to original sources
PubMed2005

On Myosin II dynamics in the presence of external loads.

We address the controversial hot question concerning the validity of the loose coupling versus the lever-arm theories in the actomyosin dynamics by re-interpreting and extending the phenomenological washboard potential model proposed by some of us in a previous paper. In this new model a Brownian motion harnessing thermal energy is assumed to co-exist with the deterministic swing of the lever-arm, to yield an excellent fit of the set of data obtained by some of us on the sliding of Myosin II heads on immobilized actin filaments under various load conditions. Our theoretical arguments are complemented by accurate numerical simulations, and the robustness of the model is tested via different choices of parameters and potential profiles.

Actins↗
PubMed2004

Detection of HLA class II-dependent T helper antigen using antigen phage display.

Major histocompatibility complex (MHC) class II-dependent antigens not only activate CD4+ T helper (Th) cells, but also cytolytic T lymphocytes and effector cells of the innate immune system. These antigens therefore are candidate vaccines against cancer and infectious agents. We have developed a novel approach using a model antigen, tetanus toxoid (TT), which provides the basis for the establishment of a novel strategy of cloning Th antigens. In the TT model system, a cDNA library encoding part of the TT light chain which contained a TT-associated Th epitope recognized by TT-specific Th clones was displayed on a phage vector (TT-phage) and presented to TT-specific Th cells by autologous Epstein-Barr virus-transformed B cells (APC). These TT-phages were able to specifically activate two different TT-specific CD4+ Th cell lines as demonstrated both in [3H]thymidine incorporation and cytokine release assays. Th cell stimulation by TT-phages was significant at a ratio of one TT-phage in 50 irrelevant phages. The described approach provides the basis for the development of a novel strategy of cloning MHC class II-dependent Th antigens, using available Th cells. This strategy has several potential advantages over existing antigen cloning methods or biochemical peptide isolation.

Antigen Presentation↗
PubMed2001

Association of the apolipoprotein E epsilon4 allele with late-onset depression.

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer's disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE epsilon4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE epsilon4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE epsilon4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0-14.0) or LOD (OR = 6.1, 95% CI, 1.9-19.0) than of EOD (OR = 0.7, 95% CI, 0.2-2.5). These results suggest an association between the ApoE epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.

Age of Onset↗
PubMed2000

Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?

Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimer's disease (AD) and 51 non-demented controls were measured. To investigate the cellular activation of peripheral immune system, plasma levels of neopterin were also investigated. Plasma levels of IL-1 were detectable in 17 patients with AD (13%) and only in one control (2%) and average levels of IL-1 were higher in AD patients than in controls (p < 0.001). IL-6 plasma levels were detectable in a higher proportion of AD and controls (53% and 27%, respectively), and were increased in patients with AD (p < 0.001). Plasma levels of ACT were increased in patients with AD (p < 0.001) and CRP levels were in the normal range. Plasma levels of neopterin were slightly lower in AD patients than in controls, but differences were not statistically significant. No significant correlation was observed between IL-1 and IL-6 levels or neopterin and cytokine levels in plasma from AD patients. Plasma levels of ACT negatively correlated with cognitive performances, as assessed by the mini mental state examination (MMSE; R = -0.26, p < 0.02) and positively correlated with the global deterioration state (GDS) of AD patients (R = 0.30, p < 0.007). Present findings suggested that detectable levels of circulating cytokines and increased ACT might not be derived by activation of peripheral immune system of AD patients. Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD.

Aged↗
PubMed2000

The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer's disease.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43 non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut-off point for being considered as responsive to tacrine treatment was a 4-point decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers to respond better than the epsilon4+ carriers. When patients were stratified by gender, no differences were found between the effects of the treatment on men and women. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to tacrine in AD patients.

Aged↗
PubMed1999

Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease.

Controversy exists regarding the apolipoprotein E (ApoE) epsilon4 allele association with vascular dementia (VaD), ranging from increased epsilon4 frequency, similar to that found for Alzheimer's disease (AD), to no association between the epsilon4 allele and VaD. To clarify further the relationship between ApoE alleles polymorphism and cerebrovascular disease (CVD) in demented and cognitively impaired patients, we examined the ApoE phenotypes in a sample of 280 patients: 155 with AD, 21 with VaD, 32 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) but without CVD, and 27 in which vascular disease was the most probable cause of cognitive decline [vascular mild cognitive impairment (VMCI)]. Our results show that the frequency of the ApoE epsilon4 allele in patients over 70 years old with clinically diagnosed VaD and VMCI does not differ significantly from that of controls. In contrast, ApoE epsilon4 allele-bearing individuals had greater risk of having late-onset AD (OR = 8.8; 95% CI 3.7-21.0), or non-vascular cognitive impairment (OR = 7.0; 95% CI 2.5-19.0).

Aged↗
PubMed1998

Hepatitis G virus infection in the elderly.

BACKGROUND AND AIMS: At least 10% of post-transfusion and community-acquired hepatitis cases are not accounted for by the A to E viruses. Hepatitis G virus (HGV), a novel agent belonging to the Flaviviridae and distantly related to HCV has recently been identified. The epidemiology and clinical significance of this infection in the geriatric setting is still little known. Aim of the investigation was to assess the prevalence and clinical significance of HGV infection in the geriatric setting. PATIENTS: 105 unselected consecutive patients (mean age 73.4 years). METHODS: HGV-RNA was detected by a single-tube reverse-transcription heminested polymerase chain reaction with primers from the 5' untranslated region of the virus. Anti-HGV antibodies were detected with a commercial anti-E2 immunometric assay. RESULTS: 3/105 patients (2.9%) were viraemic, without a history or clinical evidence of hepatitis. Anti-HGV antibodies were detected in 25 patients (23.8%), 40% of whom had associated anti-HCV antibodies. The presence of HGV-RNA and anti-HGV antibodies was mutually exclusive. CONCLUSIONS: HGV infection is highly prevalent in our population and the cumulative risk of exposure is proportional to age. In most cases, HGV infection is self-limiting and clinically irrelevant. Immunity against E2 or other associated uncharacterized viral epitopes appears to be protective.

Age Distribution↗
PubMed1997

Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to stimulation with angiotensin II.

The aim of this study was to investigate the roles of angiotensin II (Ang II) receptor subtypes 1 (AT1) and 2 (AT2) in producing vascular wall hypertrophy and qualitative changes in smooth muscle cell gene expression. Wistar rats were treated for 23 days with osmotic minipumps containing solvent and either Ang II (120 ng.kg-1.min-1) or PD123319 (30 mg.kg-1.d-1), an AT2 receptor antagonist. In addition, rats receiving solvent and either Ang II or PD123319 were given losartan, an AT1 receptor antagonist, in the drinking water (10 mg.kg-1.d-1). Vascular wall hypertrophy and smooth muscle phenotype were characterized by morphometric analysis combined with immunohistochemistry. Ang II-induced hypertension was associated with the development of medial hypertrophy of the aorta and coronary arteries accompanied by reversion of vascular smooth muscle cells (VSMCs) toward an immature phenotype, as shown by the expression of cellular fibronectin and nonmuscle myosin. Losartan treatment, which restored normal arterial pressure, prevented all these changes. PD123319 treatment, which had no effect on blood pressure, prevented only vascular hypertrophy, with no effect on VSMC phenotype. Administration of only losartan to normal rats reproduced the Ang II-induced vascular hypertrophy, with no effect on VSMC phenotype. Taken together, these results suggest that (1) the trophic effect of Ang II on VSMCs is mediated via AT2 receptor subtypes and (2) changes in VSMC phenotypes are triggered mainly through AT1 receptor subtypes.

Angiotensin II↗
PubMed1996

Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure.

Angiotensin II (Ang II) is both a vasoactive and a potent growth-promoting factor for vascular smooth muscle cells. Little is known about the in vivo contribution of AT1 and AT2 receptor activation to the biological action of Ang II. Therefore, we investigated the effect of AT1 or AT2 subtype receptor chronic blockade by losartan or PD123319 on the vascular hypertrophy in rats with Ang II-induced hypertension. Normotensive rats received for 3 wk subcutaneous infusions of Ang II (120 ng/kg per min), or Ang II + PD 123319 (30 mg/kg per d), or Ang II + losartan (10 mg/kg per d) or PD 123319 alone, and were compared with control animals. In normotensive animals, chronic blockade of AT2 receptors did not affect the plasma level of angiotensin II and the vascular reactivity to angiotensin II mediated by the AT1 receptor. Chronic blockade of AT1I in rats receiving Ang II resulted in normal arterial pressure, but it induced significant aortic hypertrophy and fibrosis. Chronic blockade of AT2 receptors in Ang II-induced hypertensive rats had no effect on arterial pressure, but antagonized the effect of Ang II on arterial hypertrophy and fibrosis, suggesting that in vivo vasotrophic effects of Ang II are at least partially mediated via AT2 subtype receptors.

Angiotensin II↗
PubMed1996

Medulloblastoma in children: CT and MRI findings.

Our purpose was to determine whether medulloblastoma (MB) shows specific neuroradiological features which may be employed in differential diagnosis from other common posterior cranial fossa tumours in childhood. Preoperative MRI was performed on 20 children with MB, and preoperative CT in 17 of them. All underwent surgery and histopathological diagnosis. There was a constant relationship between high density on CT and low signal on T1-weighted images. Signal behaviour on T2-weighted images and the degree of contrast enhancement were more variable. Most tumours arose in the midline, from the cerebellar vermis, involving the fourth ventricle, but hemisphere and extra-axial neoplasms were also seen. The combination of high density on CT and low signal on T1-weighted images is highly suggestive of MB and may assist preoperative differential diagnosis from other posterior cranial fossa tumours.

Adolescent↗
PubMed1995

Angiotensin II increases cGMP content via endothelial angiotensin II AT1 subtype receptors in the rat carotid artery.

Angiotensin II (Ang II) has been reported to modulate cGMP formation in various types of cells. To acquire direct information on the intracellular transduction involved in this mechanism, we tested the effects of Ang II on vascular tone and on cGMP content of in vitro isolated carotid arteries from 12-week-old Wistar-Kyoto rats. Segments of carotid artery 20 mm long (n = 8 for each group) maintained at a transmural pressure of 100 mm Hg were immersed in a bath (38 degrees C) containing oxygenated Tyrode's solution. At the end of each experiment, the vessel diameter was measured, and the wall cGMP content was determined by enzyme immunoassay. Under basal conditions, mean diameter was 968 +/- 19 microns, and mean cGMP carotid artery content was 38.9 +/- 3.5 fmol/mg tissue. Incubation for 20 minutes with Ang II (10(-5) mol/L) significantly increased cGMP wall content, twofold above the basal content (P < .01), and constricted the vessel (60 +/- 2.2% of the control diameter, P < .001). After preincubation with a nonselective antagonist of Ang II receptors, saralasin ([Sar1,Val5,Ala8]Ang II, 5 x 10(-5) mol/L), or with a specific antagonist of Ang II AT1 receptor subtype, losartan (5 x 10(-5) mol/L), carotid diameter and cGMP content were no longer affected by Ang II. Exposure of carotid arteries to a specific antagonist of Ang II AT2 receptor, PD 123319 (10(-7) mol/L), modified neither Ang II-induced diameter decrease nor cGMP content increase. Constriction of the vessel with KCl (26 +/- 3%, P < .001) did not modify the basal cGMP wall content.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Endothelial AT1-mediated release of nitric oxide decreases angiotensin II contractions in rat carotid artery.

The purpose of this study was to examine whether angiotensin II (Ang II) stimulates the release of endothelium-derived nitric oxide, which then impairs the contractions of vascular smooth muscle caused by the peptide, and to determine the receptor subtypes mediating these responses. Experiments were performed on isolated rings of rat carotid artery either incubated in the presence of phosphodiesterase inhibitor for the measurement of intracellular levels of cGMP or suspended in organ chambers for recording of changes in isometric force. Ang II (10(-7) mol/L) caused a twofold increase in intracellular cGMP level in preparations with but not in those without endothelium. The presence of endothelium impaired the contractions evoked by the peptide and caused approximately 50% inhibition of the maximal response to Ang II (3 x 10(-8) mol/L); pD2 values for Ang II were 8.9 +/- 0.1 and 9.6 +/- 0.2 in rings with and without endothelium, respectively. In rings with endothelium the contractions to Ang II were augmented by nitro-L-arginine (an inhibitor to nitric oxide synthase) but not indomethacin (an inhibitor of cyclooxygenase), to reach a response comparable to that of preparations without endothelium. In rings without endothelium losartan (a preferential angiotensin type 1 receptor antagonist) displayed competitive antagonism toward Ang II (pA2 = 9.5); PD 123319 (a preferential angiotensin type 2 receptor antagonist; up to 10(-7) mol/L) did not affect the response to the peptide. Losartan (3 x 10(-9) mol/L) but not PD 123319 (10(-7) mol/L) impaired the endothelium-dependent component of the response to the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Control of carotid vasomotor tone by local renin-angiotensin system in normotensive and spontaneously hypertensive rats. Role of endothelium and flow.

To investigate the relation between the tissue renin-angiotensin system (RAS) and the local vasomotor tone of large arteries, we used in vitro isolated carotid arteries from 14-week-old Wistar-Kyoto rats (WKY; n = 80) and spontaneously hypertensive rats (SHR; n = 80). Diameters were measured with the use of an ultrasonic echo-tracking system (12 MHz) under flow (2 mL/min) (F+) or no-flow (Fo) conditions, with intact endothelium (Endo+) or after endothelium removal (Endo-). The role of tissue RAS was assessed by incubating isolated carotid arteries with an angiotensin-converting enzyme inhibitor (ACE I; lisinopril, 10(-6) mol/L) or with a specific antagonist of angiotensin II AT1 receptors (AT1A; losartan, 10(-6) mol/L). In addition, maximal dilation of carotid arteries was measured after poisoning with KCN (100 mg/L). In all experiments, KCN significantly increased carotid diameters (WKY, 23 +/- 0.9%; SHR, 19 +/- 0.8%; P < .001 versus control conditions). In intact carotid arteries, flow caused significant dilation in WKY (7 +/- 0.5%, P < .001) but had no effect in SHR. In the presence or absence of flow, ACE I and AT1A induced similar dilations in both strains, and a specific antagonist of bradykinin B2 receptors (Hoe 140, 10(-7) mol/L) had no effect on ACE I-induced dilation. After endothelium removal, carotid artery diameters were significantly increased (P < .001) in both strains, although more in SHR (13 +/- 0.8%) than in WKY (8 +/- 1.1%) (P < .001). Also, flow did not modify the diameter of deendothelialized vessels and ACE I had no effect in either strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

In vitro assessment of diameter-pressure relationship in carotid arteries from normotensive and spontaneously hypertensive rats.

OBJECTIVE: To compare the mechanical properties of carotid arteries from normotensive and spontaneously hypertensive rats. DESIGN: The pressure-diameter relationships of carotid arteries from nine normotensive adult Wistar-Kyoto (WKY) and nine spontaneously hypertensive rats (SHR) were measured in vitro under control conditions and after poisoning the smooth muscle cells with potassium cyanide. METHODS: Changes in diameter due to changes in transmural pressure were determined with an ultrasonic dimensiometer (12 MHz). The diameter values were determined from the transit times of the pair of echoes given by the proximal and distal walls. The carotid artery was submitted to stepwise increases in pressure of 25 mmHg, from 0 to 200 mmHg; each pressure level was maintained for 5 min before the arterial diameter was recorded. RESULTS: The carotid artery pressure-diameter relationship was a sigmoid curve in both strains. At the same level of pressure, the diameter of the carotid artery from SHR was significantly larger than that from normotensive rats (P < 0.05). Furthermore, the diameter values measured at the operating mean arterial pressure (roughly 100 mmHg for WKY rats and 150 mmHg for SHR) were markedly different (P < 0.001). In both strains, the diameter under passive conditions (with potassium cyanide) was significantly larger than that measured under control conditions (P < 0.01). CONCLUSIONS: Carotid arteries from SHR were significantly stiffer than those from WKY rats. Due to the pressure-dependency of the arterial wall stiffness, the increased arterial stiffness reported in hypertensive rats in vivo is related to an increase in distending arterial pressure and also to a significant reduction in the intrinsic compliance of the arterial wall.

Animals↗
PubMed1992

Iatrogenic bile duct injuries. The real incidence and contributing factors--implications for laparoscopic cholecystectomy.

Laparoscopic cholecystectomy has achieved wide acceptance as the preferred treatment for symptomatic gallbladder disease. Yet there are alarming reports of iatrogenic bile duct injuries. To establish a comparison standard, the incidence of iatrogenic bile duct injury during conventional cholecystectomy has to be known. A single institutional retrospective review of 1,617 consecutive open cholecystectomies between 1980 and 1989 was performed. Eight patients (0.49%) sustained iatrogenic bile duct injury in this study. Inflammation, anatomic variation, or both were contributing factors in all injuries. Operative cholangiography identified the injury at the initial operation in three patients. Treatment consisted of either primary ductal repair, ductal repair over a stent, or ductal-enteric anastomosis. There were no late complications after surgery (follow-up 26 to 97 months; mean 50.9 months). The implications for laparoscopic cholecystectomy are apparent. Iatrogenic bile duct injuries are associated with acute inflammation and/or variant ductal anatomy; routine operative cholangiography assumes increased importance; and immediate repair of the injury minimizes long-term complications.

Acute Disease↗
PubMed1989

The dulling of twist drills during pin channel placement.

Dull twist drills used for pin channels have been cited as an etiology for dentinal cracks. This investigation examined the dulling phenomenon after repeatedly using twist drills. Inspection of the twist drills in the SEM for metal deformation revealed no alteration of the cutting edges but an accumulation of a smear debris was noted behind the cutting edges of the cone-shaped drill. Debris was also recorded on the land and flute spiral surfaces with morphological changes on the dentinal walls. These surfaces progressed serially from a rough surface to a smooth, plaque-like surface with fine striations oriented toward the drill rotation. The timing of the changes coincided with dentinal cracking reported by others. Dulling of twist drills in dentin can be attributed to adherence of byproducts rather than a loss of the cutting edge.

Dental Instruments↗