Biomedical subjects

N Guerra

Publications and source records attributed to N Guerra.

At least 19 recordsLinked to original sources

PubMed2003

Soluble proteins of chemical communication in the social wasp Polistes dominulus.

Members of the odorant-binding protein (OBP) and chemosensory protein (CSP) families were identified and characterised in the sensory tissues of the social wasp Polistes dominulus (Hymenoptera: Vespidae). Unlike most insects so far investigated, OBPs were detected in antennae, legs and wings, while CSPs appeared to be preferentially expressed in the antennae. The OBP is very different from the homologous proteins of other Hymenopteran species, with around 20% of identical residues, while the CSP appears to be much better conserved. Both OBP and CSP, not showing other post-translational modifications apart from disulphide bridges, were expressed with high yields in a bacterial system. Cysteine pairing in the recombinant and native proteins follows the classical arrangements described for other members of these classes of proteins. OBPs isolated from the wings were found to be associated with a number of long-chain aliphatic amides and other small organic molecules. Binding of these ligands and other related compounds was measured for both recombinant OBP and CSP.

Amino Acid Sequence↗

PubMed2003

Relationship between CDC cross-match in liver recipients and antibody screening by flow cytometry.

Several authors have shown that anti-donor antibodies before liver transplantation are associated with decreased graft survival. The aim of this study was to investigate the relationship between anti-donor antibodies detected by the CDC technique or by FlowPRA, and acute or chronic rejection as well as graft survival. Furthermore, we sought to determine whether anti-donor antibodies, detected by the CDC technique, correlated with those discovered by cytometric screening. The acute rejection incidence among patients with complement-dependent cytotoxicity positive CDC cross-match was similar to that for patients with a negative cross-match. None of the patients with a positive cross-match developed chronic rejection. Allograft survival was significantly lower among recipients with a positive T-lymphocyte cross-match. Indeed, the majority of recipients with positive CDC cross-matches displayed graft failures before first posttransplant year. The results of a positive FlowPRA determination were concordant with a positive CDC cross-match in 85.71% of cases. Our data demonstrate that pretransplant FlowPRA correlates with the final CDC cross-match results. This finding suggests that in the future prospective pretransplant antibody screening with FlowPRA or CDC techniques may be useful to identify high-risk recipients.

Acute Disease↗

PubMed2002

Tumor escape from killing: role of killer inhibitory receptors and acquisition of tumor resistance to cell death.

Immunotherapy of cancer has always been a very attractive fourth-modality therapeutic approach. Over the past few years, advances in the identification of tumor antigens have offered new perspectives and provided new opportunities for more accurate immunotherapy for cancer. However, when applied to patients with established tumors, it rarely leads to an objective response. This is partly due to the fact that tumors evade host immunity at both the induction and effector phases. Thus, understanding tumor escape mechanisms may be the key to successful immunotherapy for cancer. In the present review, we will focus on how the expression of killer Ig receptors (KIR) on tumor infiltrating lymphocytes can compromise their function and how tumors evade apoptotic death - two additional mechanisms of tumor escape.

Apoptosis↗

PubMed2001

Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma.

HLA-G is a nonclassical class I antigen mainly expressed at the maternofetal interface during pregnancy where it is thought to down-modulate maternal immune response against the semiallogeneic fetus. Recent studies indicate that ectopic up-regulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investigated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antigen is differentially expressed in carcinoma and normal renal cells and that up-regulation of this antigen in the tumor cells is more frequent than alterations of other MHC class I or class II antigens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (alpha and beta) and, in particular, type II (gamma) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suggest that HLA-G displays various functional features that allow down-modulation of immune response in vitro, we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.

Adult↗

PubMed2001

Tumor cells regulate the lytic activity of tumor-specific cytotoxic t lymphocytes by modulating the inhibitory natural killer receptor function.

Tumor-infiltrating p58+ T cells from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned. These p58+ T cells were found to express a memory phenotype and corresponded to clonal TCRBV3 T-cell expansion. Functionally, p58(+) CTLs displayed a low lytic activity for HLA-A2 tumor and normal cells. However, this lytic activity was significantly increased after blockade of p58 with specific monoclonal antibodies. Interestingly, we demonstrated that stimulation by tumor cells was required to trigger the inhibitory effect of p58 on the lytic activity of antigen-specific CTLs and that stimulation of the inhibitory function of p58 by tumor cells correlated with an inhibition of nuclear factor-kappaB activation in p58+ tumor-specific CTLS.

Antibodies, Monoclonal↗

PubMed2001

[Technological advances in immuno-oncology: from fundamental concepts to patient immunological monitoring].

Over the past decade, cancer immunology has known several advances due to both basic research and new technologies recently developed in this field. This review will illustrate the impact of some new immunological technologies and how the latter resulted in the exploration of new territories in cancer immunology and the emergence of new concepts that allowed to revisit the immunosurveillance concept and permitted to improve the patient monitoring.

Antigens, Neoplasm↗

PubMed2000

Use of embryonic human trachea grown in nude mice to patch-repair congenital tracheal stenosis.

BACKGROUND: Long congenital tracheal stenosis is a life-threatening condition, and the available surgical treatments do not give satisfactory long-term results. METHODS: Human embryonic tracheas were implanted in the abdominal cavities of nude mice until their differentiation was completed. These differentiated tracheas were used to patch-repair surgically induced tracheal stenosis in piglets. The human, mouse, or pig origin, of all the cells in the two successive xenotransplants in the nude mouse and the pig, was determined on tissue sections by in situ hybridization with species-specific DNA probes. RESULTS: The transplanted pigs thrived and reached normal adulthood, irrespective of the administration of immunosuppressive treatment. The human tracheal tissue developed in nude mice conserved human structures, with the exception of feeding capillaries, which were of mouse origin. The tracheal patch in the adult healthy pigs comprised only pig cells organized into a fibrous scar, which was covered by normal pig epithelium. CONCLUSIONS: Results suggest that human embryonic trachea grown in nude mice can be successfully used as patch tracheoplasty for long congenital tracheal stenosis without conventional immunosuppression.

Animals↗

PubMed2000

Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas.

In this study, we showed that renal tumors contain substantial subsets of CD8(+) p58(+) T cells. From 1 of these tumors, T cells were amplified in mixed lymphocytes-tumor cell cultures and p58(+) T cells were selected immunologically. After expansion, phenotypic and functional features of p58(+) and p58(-) T cells were examined. The p58(+) T cells expressed p58.2 receptor and corresponded to CD3(+), CD8(+), T-cell receptor (TCR) alpha/beta(+) T cells that were CD56(+) and CD28(-). Functionally, p58(+) T cells showed a low level of lytic activity against autologous tumor cells that was dramatically and specifically increased by anti-p58.2 monoclonal antibody. On the other hand, p58(-) CD8(+) T cells did not lyse autologous tumor cells and had non-major histocompatibility complex-restricted cytotoxicity against K562 and Daudi cells. A p58(+) cytotoxic T lymphocyte (CTL) clone (4C7) with the same characteristics as the p58(+) T-cell line was derived. This CTL clone did not lyse autologous normal B cells but lysed several HLA-A1(+) renal tumor cell lines. Analysis of TCR repertoire diversity showed that the p58(+) T-cell line contained 3 TCR rearrangements, whereas the TCR repertoire of p58(-) T cells was polyclonal. Interestingly, TCR transcripts of p58(+) T cells and of CTL clone 4C7 were detected as prominent ex vivo in tumor cells but not in peripheral blood mononuclear cells, suggesting that these cells are antigen specific and amplified at the tumor site. (Blood. 2000;95:2883-2889)

Antigens, CD↗

PubMed2000

Kinetic analysis of microchimerism induced by intrathymic injection of allogeneic splenocytes in mice.

Allograft survival facilitated by intrathymic (i.t.) injection of allogeneic cells have shown that modifications of T-cell development induce specific tolerance. One hypothesis is that the resulting microchimerism may play a role in preparing the host immune system for the allograft. To investigate whether the deliberate introduction of allogeneic splenocytes into the thymus of adult mice allows the establishment of a lasting donor/recipient microchimerism, a full allogeneic mouse system (H-2 and Mls) with additional sex mismatch was used. Male cells injected into female mice were detected using an optimized nested-polymerase chain reaction which specifically amplifies the SRY gene with a sensitivity of 1/10(4). After i.t. injection, donor cells were observed early both in the lymph nodes and spleen (75 and 25% of mice, respectively). They were still present on day 6, although preferentially in the thymus (100% of mice) than in the lymph nodes (50% of mice) or in the spleen (22% of mice). After intraperitoneal (i.p.) or subcutaneous (s.c.) injection, donor cells were early (2 h) but transiently detected in the thymus, since on day 6 they were detected in 0 and 17% of mice after i.p. and s.c. injection, respectively. Kinetics of donor-cell detection was similar both in the spleen and lymph nodes with a clear decrease in the percentage of mice with donor-cell detection between day 2 and day 6 (20 and 17% of positive mice for the spleen after i.p. and s.c. injections, respectively--20 and 33% of positive mice for the lymph nodes after i.p. and s.c. injections, respectively). Our results clearly show that i.t. injection of allogeneic splenocytes induces a microchimerism which is both more lasting and detected in a higher percentage of mice than by the i.p. and s.c. routes, both at the central (thymus) and peripheral (spleen) levels.

Animals↗

PubMed2000

Normative influences on aggression in urban elementary school classrooms.

We report a study aimed at understanding the effects of classroom normative influences on individual aggressive behavior, using samples of 614 and 427 urban elementary school children. Participants were assessed with measures of aggressive behavior and normative beliefs about aggression. We tested hypotheses related to the effects of personal normative beliefs, descriptive classroom norms (the central tendency of classmates' aggressive behavior), injunctive classroom normative beliefs (classmates' beliefs about the acceptability of aggression), and norm salience (student and teacher sanctions against aggression) on longitudinal changes in aggressive behavior and beliefs. injunctive norms affected individual normative beliefs and aggression, but descriptive norms had no effect on either. In classrooms where students and teachers made norms against aggression salient, aggressive behavior diminished over time. Implications for classroom behavior management and further research are discussed.

Adolescent↗

PubMed2000

Giant intracranial aneurysm of the anterior communicating artery treated by direct surgical approach. Case report.

We report the singular case of an exceptionally large giant communicating artery aneurysm successfully treated with a direct surgical approach. The clinical presentation was a relatively short history of frontal headache. In the pre- and postcontrast CT scans the lesion mimicked an intracranial tumor. At surgery the intraluminal thrombus was partially removed with an ultrasonic surgical aspirator; the decompression allowed the isolation and subsequent temporary dipping of the tracts A1 and A2 of both the anterior cerebral arteries. It was then possible to complete the thrombectomy and to dip the neck of the aneurysm. The report emphasizes the indispensable role of MRI for the accurate diagnosis of giant intracranial aneurysms and the recent improvement of the surgical results concerning this category of aneurysms (mainly related to the present wider availability of technical surgical instrumentation).

Carotid Arteries↗

PubMed1999

Verapamil reduces dipyridamole-induced myocardial ischemia in patients with coronary artery disease.

The aim of this study was to evaluate the effects of verapamil administration on dipyridamole-induced transient wall-motion abnormalities as detected by two-dimensional echocardiographic monitoring in patients with coronary artery disease. Twenty-eight patients (16 men and 12 women; mean age, 60+/-7 years) with angiographic evidence of significant coronary artery disease, positive dipyridamole echocardiography test results at basal condition on two consecutive days, were prospectively studied. Patients were randomized to verapamil (360 mg/day) or placebo treatments, given in three divided doses daily for 7 days; at the end of this time, each patient crossed over to the alternate regimen. Dipyridamole echocardiographic testing was repeated at the end of each treatment period. Our data demonstrate that verapamil significantly reduces the dipyridamole-induced wall-motion score index, a quantitative marker of acute myocardial ischemia (1.7+/-0.4 vs. 1.3+/-0.2; p<0.001). Hemodynamic data show that the drug reduces heart rate and rate-pressure product at basal condition (heart rate from 75+/-8 to 67+/-9 beats/min; p<0.001; rate-pressure product from 99+/-13 to 86+/-13 U x 10(-2); p<0.001) and at peak dipyridamole infusion (heart rate from 96+/-8 to 89+/-6 beats/min; p<0.001; rate pressure product from 127+/-21 to 118+/-13 U x 10(-2); p<0.05) with respect to placebo treatment. We conclude that verapamil is able to reduce dipyridamole-induced ischemia, as detected by two-dimensional echocardiographic monitoring, in patients with coronary artery disease by reducing, at least partially, myocardial oxygen consumption. Moreover, its beneficial action could be related to the effects of the drug on coronary collateral circulation and on sympathetic modulation.

Aged↗

PubMed1999

Effect of tumor growth factor-beta on NK receptor expression by allostimulated CD8+ T lymphocytes.

We have examined the influence of the immunosuppressive cytokine TGF-beta on NK receptor expression by T lymphocytes upon allogeneic activation. Using the primary mixed lymphocyte reaction (MLR), our data show that allostimulation induced the expression of CD94/NKG2-A on alloactivated CD8+ T cells. This expression was increased in the presence of TGF-beta whereas IL-15 had no significant effect. The blockage of CD94 and NKG2-A resulted in increased lysis of targets by alloactivated cytotoxic T cells. This increase was dependent on the activation state of T cells. Using PCR, we also demonstrated that TGF-beta had no effect on the transcription of non-inhibitory NKG2 molecules. The present results show that allostimulation can induce CD94 and further point out the role of TGF-beta in the induction of the CD94/NKG2-A receptor on alloactivated T cells.

Antigens, CD↗

PubMed1995

Failure of protective effect of captopril and enalapril on exercise and dipyridamole-induced myocardial ischemia.

Fifteen patients with angiographic evidence of significant coronary artery disease, exertional myocardial ischemia, and positive dipyridamole echocardiographic test results at basal conditions and after 7 days of placebo treatment were prospectively studied to see whether captopril (containing sulfhydryl) and enalapril (nonsulfhydryl) modify myocardial ischemia induced by exercise testing and the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to captopril (150 mg/day in 3 separate doses) or enalapril (20 mg/day) for 1 week. At the end of this period each patient crossed over to the alternate regimen after a washout period of 7 days. Exercise stress testing and dipyridamole echocardiographic testing were repeated at the end of each treatment period. Neither captopril nor enalapril had a significantly greater anti-ischemic effect than placebo in any patient. Exercise duration, time to onset of ST-segment depression, maximal workload, degree of ST-segment depression, and rate-pressure product were not affected by either drug. Neither captopril nor enalapril improved dipyridamole-induced mechanical dysfunction or ST-segment depression.

Adult↗

PubMed1995

Age-response effectiveness of gallopamil for the treatment of myocardial exertional ischemia. A medium-term randomized cross-over double-blind placebo-controlled trial.

We evaluated the efficacy and safety of gallopamil 150 mg daily in middle-aged and elderly patients with stable exertional ischemia, using a medium-term randomized double-blind cross-over placebo-controlled trial. Twenty middle-aged patients (52.8 +/- 6 years; range 38-61 years) and 14 elderly patients (67.4 +/- 2.8 years; range 65-73 years) with stable exertional ischemia underwent a bicycle exercise test. After a run-in period, both groups received treatment with either placebo or gallopamil 50 mg tid for 28 days. At the end of this time, each patient crossed over to the alternate regimen. Gallopamil significantly reduced heart rate, blood pressure and rate pressure product (from 15.37 +/- 2.7 to 13.65 +/- 4.16 U x 10(-3); p < 0.01) in elderly patients at submaximal exercise, but had no effect in middle-aged patients (from 14.52 +/- 4.45 to 13.49 +/- 3.77 U x 10(-3); p = NS). At peak exercise, none of the hemodynamic parameters was modified with gallopamil in either group. At peak exercise, both middle-aged and elderly patients achieved rate-pressure products similar to those reached during placebo at higher work loads. Exercise duration and maximal work load significantly increased in both groups. Electrocardiographic signs of ischemia were favorably influenced by gallopamil in both groups (from 1.39 +/- 0.5 mm to 0.76 +/- 0.73 mm; p < 0.001 in the middle-aged patients and from 1.5 +/- 0.34 mm to 1 +/- 0.76 mm; p < 0.01 in the elderly patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Age-related changes of antianginal effects of verapamil in patients with stable effort angina. A medium term randomized double-blind placebo controlled trial.

Our study evaluated the effects of verapamil in elderly patients with stable effort angina using a medium-term double-blind placebo-controlled protocol. Thirty-nine consecutive patients, 23 middle-age patients (50 +/- 6 years; range 38-60 years) and 16 elderly patients (66 +/- 2 years; range 65-70 years) with exertional angina were chosen. After a run-in period, both groups received treatment with either placebo or verapamil--360 mg daily--for 4 weeks. During treatment, weekly angina frequency and nitroglycerin consumption were significantly reduced in both groups. Verapamil significantly decreased the rate-pressure product at rest in elderly patients and in both groups at submaximal exercise, due to a reduction in heart rate in both groups and to a more marked decrease in arterial pressure in older patients. At peak exercise, the rate-pressure product was unchanged in both groups after verapamil, while exercise capacity showed a significant improvement in the middle-aged, and ST segment depression was reduced in both groups. After verapamil, 30% of middle-aged patients and 44% of elderly patients had to stop exercising because of angina. Side effects were rare and no drop-out was recorded. Verapamil exerted its antianginal action by means of a decrease in myocardial oxygen consumption at rest and at submaximal exercise in the elderly, while only at submaximal exercise in the middle-aged. Therefore verapamil at the dose of 360 mg daily proved an effective antianginal drug with a safe effect profile also in elderly patients.

Adult↗

PubMed1992

Safety and immunogenicity of acellular diphtheria-tetanus-pertussis and Haemophilus conjugate vaccines given in combination or at separate injection sites.

This prospective, double-blind, randomized trial compared the immunogenicity and reactogenicity of acellular diphtheria-tetanus-pertussis vaccine and Haemophilus influenzae type b conjugate vaccine-diphtheria toxoid conjugate, given at separate injection sites or at a single site, in 79 children 18 months of age who had received three prior immunizing doses of whole-cell diphtheria-tetanus-pertussis vaccine. No significant differences were observed.

Antibodies, Bacterial↗

PubMed1992

Duration of rifampin chemoprophylaxis for contacts of patients infected with Haemophilus influenzae type B.

Rifampin is recommended as a prophylactic treatment for intimate contacts of young children who develop invasive infections with Haemophilus influenzae type B (Hib). A 4-day course of rifampin (20 mg/kg of body weight per day, not to exceed 600 mg as a maximum single daily dose) is 95% effective in eradicating pharyngeal colonization with Hib, thus effectively reducing the risk of both associated patients and recurrent illness in index patients less than 2 years old. This study compares rates of eradication of pharyngeal colonization with Hib for 2- and 4-day courses of rifampin therapy. One hundred sixty-three patients with Hib infection were treated at Children's Hospital of Pittsburgh between January 1986 and December 1988; prophylaxis was recommended for 128. Participating families were randomized to receive either 2- or 4-day therapy. Throat swabs were obtained from contacts prior to therapy. Repeat cultures were obtained from colonized contacts 2 days after completing rifampin and again on all contacts 7 to 10 days after completing therapy. Of 68 participating families, 34 received 2-day and 34 received 4-day therapy with rifampin. Twenty-two of 24 colonized contacts in the 2-day group and 17 of 18 in the 4-day group had negative cultures for Hib on follow-up. Two-day therapy with rifampin appears to be as effective as 4-day treatment in the eradication of Hib pharyngeal colonization.

Administration, Oral↗