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Biomedical subjects

A Giuliani

Publications and source records attributed to A Giuliani.

At least 91 records · Page 5Linked to original sources

Papillary renal cell carcinoma presenting as nodal metastases to the neck.

Renal cell carcinoma, in a high percentage of patients, metastasizes early, sometimes mimicking other lesions. We present a case of an asymptomatic papillary renal cell carcinoma that presented neck metastases as the initial manifestation. The laterocervical and supraclavicular masses were considered consistent with nodal metastases from a thyroid nodule. A hemithyroidectomy was performed before the renal tumor was diagnosed. Then the patient underwent a left-side radical nefrectomy. We discuss the unpredictability of the clinical course of renal cell carcinoma.

Aged↗

Severe bleeding from peritoneal implants of trophoblastic tissue after laparoscopic salpingostomy for ectopic pregnancy.

OBJECTIVE: To describe a case of persistent trophoblastic tissue after conservative laparoscopic treatment of an ectopic pregnancy (EP). DESIGN: Case report. SETTING: University hospital. PATIENT: A 19-year-old nulliparous woman, presenting 30 days after conservative laparoscopic treatment of an EP. INTERVENTION(S): Emergency laparotomy, histologic examination of excised trophoblastic tissue, serial beta-hCG levels. MAIN OUTCOME MEASURE(S): Serum beta-hCG clearance curves after surgical treatment of an EP. RESULT(S): Histology confirmed multiple peritoneal implants of trophoblastic tissue, mainly situated on the sigmoid colon and the omentum majus. Serial beta-hCG levels decreased rapidly from 1,394 to 0 mU/L within 17 days. CONCLUSION(S): After conservative treatment of EP, patients should be followed up clinically and serial beta-hCG measurements should be obtained to ensure the absence of persistent trophoblastic tissue.

Adult↗

Controlled ovarian hyperstimulation in assisted reproduction: effect on the immune system.

OBJECTIVE: To determine how controlled ovarian hyperstimulation (COH) in assisted reproduction affects the immune system. DESIGN: A prospective, nonrandomized, case-control study. SETTING: Academic research setting. PATIENT(S): Women with regular menstrual cycles undergoing COH in an assisted reproduction program. INTERVENTION(S): Blood samples were collected in the early and late follicular phase, at the time of ovulation, and in the luteal phase during a natural cycle, and at four times during the next cycle, which included COH and IVF. MAIN OUTCOME MEASURE(S): Lymphocyte subpopulations and the differential blood count. RESULT(S): In the natural cycles, a significant increase in the total numbers of lymphocytes, B cells, natural killer cells, and CD3+HLADR+ cells was observed in the late follicular phase, whereas the T helper/T suppressor cell ratio declined. In the hyperstimulated cycles, increases were seen in the total numbers of leukocytes and neutrophils on the day of hCG administration; the number of lymphocytes, monocytes, and neutrophils was increased on the day of oocyte retrieval, and the total number of leukocytes and neutrophils increased during the luteal phase. CONCLUSION(S): Controlled ovarian hyperstimulation with hMG and simultaneous administration of a GnRH antagonist did not affect the immune system.

Case-Control Studies↗

Effect of rifampin on CD1b expression and double-negative T cell responses against mycobacteria-derived glycolipid antigen.

Non-classical antigen-presentation by CD1 molecules expressed on cytokine-activated monocytes (CAM), and cell-mediated responses supported by double-negative (DN) and by CD8+ responder alphabeta T cells, are involved in host resistance against mycobacterial infections. The CD1b protein is responsible for presentation of non-peptide, lipid antigens to T cells. In this context, a pivotal role is played by induction of CD1b protein on the membrane of human monocytes activated by GM-CSF alone, and more efficiently by GM-CSF combined with IL-4. Rifampin (RFP), a drug which is extensively utilized for chemoprophylaxis or treatment of Mycobacterium tuberculosis, is known to reduce a number of B, or T cell-dependent responses. Therefore we undertook immunopharmacological studies on RFP, to determine the effects of this agent on human macrophage function, relative to antigen presentation by CD1b molecules and on DN T cell cytolytic function. The results showed that: (a) graded concentration of RFP (2 or 10 microg/ml) induced a significant increase of CD1b expression, in CAM as evaluated by FACS analysis; (b) RFP increased significantly the specific mAb binding to CD1b on CAM surface; (c) treatment of effector cells with RFP did not reduce DN T cell-mediated cytolysis against lymphoblastoid cells transfected with CD1b cDNA (C1R.b6 cells), pulsed with M. tuberculosis. These results suggest that RFP could be of potential value in improving mycobacterial antigen presentation without impairing responder T cell function.

Antibiotics, Antitubercular↗

Recurrence quantification analysis in structure-function relationships of proteins: an overview of a general methodology applied to the case of TEM-1 beta-lactamase.

Protein structure-function relationships have been increasingly scrutinized by a variety of correlational and information theoretic measures. In an effort to extend this methodology, a technique originally developed in non-linear science, recurrence quantification analysis, was combined with traditional principal components analysis to study a large number (56) of TEM-1 beta-lactamase mutants. The hydrophobicity profiles corresponding to the primary structure of 13 naturally occurring mutations partially impairing function, together with 43 artificial non-tolerated mutations were subjected to discriminant analysis, derived from the results of recurrence quantification analysis, coupled to a principal exponents extraction. Eleven (85%) of the naturally occurring mutants and 36 (84%) of the artificial mutants were correctly classified (p < 0.0001). We conclude that this technique may be useful in protein engineering and, in general, in structure-function studies of biopolymers.

Amino Acid Sequence↗

Rifampin increases cytokine-induced expression of the CD1b molecule in human peripheral blood monocytes.

In recent years, it has been shown that a nonclassical, major histocompatibility complex-independent system (i.e., CD1-restricted T-cell responses) is involved in T-cell immunity against nonpeptide antigens. The CD1 system appears to function by presenting microbial lipid antigens to specific T cells, and the antigens so far identified include several known constituents of mycobacterial cell walls. Among the four known human CD1 isoforms, the CD1b protein is the best characterized with regard to its antigen-presenting function. Expression of CD1b is upregulated on human blood monocytes upon exposure to granulocyte/macrophage-colony stimulating factor, alone or in combination with interleukin-4 (IL-4) (S. A. Porcelli, Adv. Immunol. 59:1-98, 1995). Rifampin (RFP) and its derivatives are widely used for chemoprophylaxis or chemotherapy against Mycobacterium tuberculosis. However, this agent was found to reduce the mitogen responsiveness of human B and T lymphocytes, chemotaxis, and delayed-type hypersensitivity. The present study extends the immunopharmacological profile of RFP by examining its effects on CD1b expression by human peripheral blood monocytes exposed to GM-CSF plus IL-4. The results showed that clinically attainable concentrations (i.e., 2 or 10 microg/ml for 24 h) of the agent produced a marked increase in CD1b expression on the plasma membrane, as evaluated by fluorescence-activated cell sorter analysis, whereas it had no effect on cytosolic fractions, as indicated by Western blot analysis. This was found to be the result of increased CD1b gene expression, as shown by Northern blot analysis of CD1b mRNA. These results suggest that RFP could be of potential value in augmenting the CD1b-restricted antigen recognition system, thereby enhancing protective cellular immunity to M. tuberculosis.

Antibiotics, Antitubercular↗

A nonlinear explanation of aging-induced changes in heartbeat dynamics.

The possibility of computing a cardiac age on the basis of spectral analysis of healthy individual tachograms was confirmed and facilitated by the use of a nonlinear technique: recurrence quantification analysis. The age of 112 subjects was predicted by this technique in terms of a progressive increase in the deterministic character of the heartbeat. This result confirms the "random-walk" character of the heartbeat as predicted by the terminal dynamics paradigm, thus allowing for a simple and comprehensive model of the effect of aging on cardiac dynamics: as age progresses, heart rate dynamics become increasingly predictable (constrained) on a beat-to-beat basis. This implies a basically stochastic nature of heart rate dynamics, probably reflecting the continuous adjustments to an unpredictable internal environment.

Adult↗

[Cervical cancer in pregnancy--practical recommendations].

Five-year survival did not differ between 20 pregnant women and 541 patients with invasive cervical cancer treated with radical surgery at the Department of Obstetrics and Gynecology of the University of Graz. Therapeutic recommendations are given. In stage Ib to IIb disease, surgery is recommended postpartum following the induction of fetal lung maturity if fertility should be preserved and if the cancer is diagnosed after the 20th week of pregnancy. The same is recommended in stage Ia independent of the duration of gestation. In advanced disease (stage IIIb to IVb) definite therapy should be applied immediately after diagnosis. If cervical intraepithelial neoplasia grade III is suspected, colposcopy, cytology and biopsy are mandatory. Definite therapy should be performed 6 weeks postpartum.

Adenocarcinoma↗

DEHP-induced alterations in the lining tissue of the rat air pouch.

The direct effects of D(2-ethylhexyl)phthalate (DEHP), on subcutaneous tissue were studied in the rat, using the air pouch technique. Two ml of DEHP either undiluted or diluted in olive oil (10 microm/ml), were introduced into a previously created air pouch in the rats. The air pouch was removed and specimens of the lining tissue examined by optical and electron microscopy. The persistence of DEHP for 7 days is sufficient to cause alterations in the tissue. The major histological changes were the destruction of the tissue organization with cytoplasmic and nuclear alterations resulting in apoptotic bodies. The histochemical data showed an increase of sulphated glycosaminoglycans, showing proof of alterations in fibroblast functions. The authors suggest that the hyperplastic-type alteration induced by DEHP may be connected with the sclerosis of the peritoneal membrane described in uremic patients in CAPD.

Administration, Cutaneous↗

Effect of the combined treatment with 5-fluorouracil, gamma-interferon or folinic acid on carcinoembryonic antigen expression in colon cancer cells.

5-Fluorouracil (5-FU) and human recombinant gamma-interferon (gamma-IFN) were found to increase the expression of carcinoembryonic antigen (CEA) in human cancer cells in vitro. In the present study, the antimetabolite was associated with gamma-IFN or folinic acid (FA), a biochemical modulator of cellular metabolism of 5-FU, able to increase its antineoplastic activity. Treatment of two human colon cancer cell lines (HT-29 and WiDr) with 5-FU + gamma-IFN resulted in an increase of CEA expression higher than that obtainable with both agents alone, although no synergistic effects were obtained. This was demonstrated in terms of: (a) mRNA transcripts (HT-29); (b) cytoplasm and membrane CEA protein levels detected by Western blot analysis (HT-29); and (c) plasma membrane reactivity determined by flow cytometry analysis (HT-29 and WiDr). Moreover, 5-FU + gamma-IFN increased HLA class I molecules in the HT-29 cell membrane over that obtainable with gamma-IFN alone. In contrast, both agents did not induce the expression of the costimulatory molecule B7-1. Treatment with FA enhanced the antitumor effect of 5-FU but not its ability to augment CEA expression. This suggests that the FA-sensitive biochemical mechanism of action of 5-FU is not involved in its effect on CEA expression. In vivo studies showed, for the first time, that 5-FU, alone or combined with gamma-IFN, increases the amount of CEA protein over controls, either in cancer cells or in peripheral blood of nude mice bearing HT-29 cells. These results could be of potential diagnostic and/or therapeutic value when CEA protein is the target of humoral or cell-mediated immunity.

Animals↗

[Circadian variation of lymphocyte subsets in health subjects].

In our study cortisol and interleukin 2 (IL-2) levels were measured and lymphocyte sub-population analyses were performed on blood samples collected every four hours, for 24 hours from 10 healthy subjects aged 38-65 years. A clear circadian rhythm was validated for cortisol serum levels, for CD8, CD8 dim, CD16 and delta TcS1 with acrophase in the morning, and for CD2, CD4, CD/CD8 ratio, HLA-DR, CD20 and CD25 with acrophase at night. CD8 bright and TcR delta 1 presented higher levels in the morning without validation of the circadian rhythm. Changes of serum levels of IL-2 did not show circadian rhythmicity. The results show that specific lymphocyte subsets present different profiles of nyctohemeral changes and this may explain time related variations of immune responses.

Adult↗

Cytokine-induced expression of CD1b molecules by peripheral blood monocytes: influence of 3'-azido-3'-deoxythymidine.

CD1b is a nonpolymorphic, MHC-like molecule, capable of presenting non-peptide antigens (Ags) to CD3+, CD4-, CD8-, alphabeta or gammadelta T lymphocytes. Previous studies have shown that CD1b can be induced in monocytes/macrophages by GM-CSF+IL-4, and can restrict their presentation of Mycobacterium tuberculosis antigen (Ag) to Ag-specific T cells. Since a number of HIV-positive subjects undergo mycobacterial infections, preliminary studies have been performed to explore whether anti-HIV chemotherapy would influence cytokine-induced CD1b expression in peripheral blood monocytes. The results obtained by treating monocytes with GM-CSF+IL-4, in presence or absence of 3'-azido-3'-deoxythymidine (AZT) showed that: (a) the majority of adherent mononuclear cells (AMNC) collected from peripheral blood of healthy donors, express CD1b molecule on the cell membrane, upon treatment with GM-CSF+IL-4; (b) CD1b appearance is mainly due to the de novo induction of CD1b gene expression (as confirmed by Northern blot analysis), rather than to migration of the molecule from the cytoplasm to the plasma membrane (as suggested by Western blot analysis); (c) AZT does not alter the percentage of CD1b+ AMNC treated with the cytokines; (d) however, AZT inhibits cytokine-induced proliferation of AMNC, thus reducing the overall Ag-presenting potential of the host. Our results suggest that the anti-proliferative effect of AZT could depress anti-mycobacteria immunity in AZT-treated subjects, which may have important implication for the clinical outcome of patients harbouring inadequately treated mycobacterial infections.

Anti-HIV Agents↗

1H NMR ganglioside ceramide resonance region on the differential diagnosis of low and high malignancy of brain gliomas.

1. The high-resolution 1H NMR (MRS) spectra of human brain tumor homogenates revealed a broad resonance at 5.3-5.4 ppm in glioblastoma multiforme (N = 16) and brain metastases (N = 3). The broad resonance was identified as ceramide, a sphingosine-fatty acid combination portion of ganglioside, indicating an elevated abundance of monounsaturated fatty acids. GLC analysis of gangliosides in the highly malignant glioblastoma multiforme revealed that the elevated monounsaturated fatty acid is oleic acid (C18:1). The resonance at 5.3-5.4 ppm region was not detectable in normal human brain (N = 2), in meningiomas (N = 2), or in low-grade astrocytomas (N = 12). In normal human brain the abundance of monounsaturated fatty acid is minimal. 2. This investigation was made possible because the method of producing homogenate resulted in (i) no loss of lipids during the process and (ii) a well-homogenised sample, with (iii) no loss in chemical integrity. 3. The properties of tumor gangliosides include antigenic specificity and immunosuppressive activity and the ceramide, a sphingosine-fatty acid combination, noticeably influences the ganglioside immunosuppressive activity. 4. The observation of 1H NMR ceramide resonance in high-malignant brain tumors emphasizes the dramatic role of aberant gangliosides and ceramide precursors on the grade of malignancy and invasiveness. 5. Further insight into the specific nature of the ceramide portion of gangliosides in grading the malignancy of brain tumors should be investigated further.

Astrocytoma↗

Free radicals, atherosclerosis, ageing and related dysmetabolic pathologies: biochemical and molecular aspects.

In human ageing and with many pathologies correlated to the senile functional decay of cells, membrane damage often occurs in some organ or tissue, which provokes lipid peroxidation in the membrane and accelerates the disorder in structure and function of the membrane. When lipid peroxides accumulate sufficiently, they leak from the organ or tissue into the bloodstream and increase the lipid peroxide level in blood lipoproteins. The increased lipid peroxides in the blood attack the blood vessel and promote atherogenesis. This paper describes the possible involvement of free radicals in this damage, both to tissues and to blood vessels, which contributes to the senile functional decay of the tissues.

Adenosine Triphosphate↗

Free radicals, atherosclerosis, ageing, and related dysmetabolic pathologies: pathological and clinical aspects.

An excess of free-radical production has been linked to many diseases and to the ageing process. Oxidant by-products of normal metabolism can cause extensive damage to DNA, protein and lipid. Exposure to ultraviolet light, cigarette smoke and other environmental pollutants may also increase the free radical burden. The accumulation of unrepaired oxidative damage products is likely to be a major factor in cellular ageing. Many repair processes are available to the cell, including enzyme and structural defences. The large group of natural antioxidants is also part of a protective mechanism. High consumption of fruit and vegetables in the diet is associated with a lowered risk of degenerative diseases. At present, however, there are few data to support the routine use of exogenous antioxidants to prevent and treat these diseases.

Aged↗

Exercise, free radical generation and vitamins.

Physical activity raises oxygen demand by many fold, causing a parallel increase in the formation of oxygen radical species. Vitamins are concerned with either energy metabolism or free radical scavenging. This review outlines the possible damage to cell structures following strenuous exercise and the role of vitamins as part of natural anti-oxidant defence systems. A brief discussion is included on the relationship between physical activity, the immune system and cancer.

Animals↗

Estimating a cardiac age by means of heart rate variability.

A data set of R-R intervals recorded for at least 15 min in 141 healthy individuals of different ages and under two different conditions ("resting" and "tilted" states) has been considered. The data have been subjected to spectral analysis by fast Fourier transform methods and considered in view of the possibility to work out a model in which the chronological and cardiac age could be compared. Understanding the results was greatly facilitated by 1) working out a number of derived variables from the original ones to highlight the presence of small but conceptually important variability factors; 2) extraction of the principal components from the original as well as from the derived variables to exclude redundancies and correlation effects; and 3) automatic clustering of the subjects in age classes, which allowed removal of individual variability within each class. The main conclusion is that, within the examined individuals, cardiac and chronological ages do not match for ages higher than approximately 50 years; this could reflect the presence of subtle (and difficult-to-envisage) biases in the data analysis or a real discrepancy. The latter hypothesis should be confirmed by similar observations in different systemic contexts. The use of a simple equation relating chronological and cardiac age, derived from a careful regression analysis on our data set and of general use for screening purposes, is demonstrated.

Adult↗

[Adenomatous tissue in colorectal carcinomas: clinical significance and probable histogenetic implications of morphological differences].

In this study we tested the hypothesis that colorectal cancers containing adenoma (CCA) could be a different entity from colon cancers without adenoma (CSA). Clinical data, histologic preparations of operative specimens and survival of 210 patients who underwent resective surgery for colorectal cancer were studied. Adenomatous tissue within the cancer was found in 62 of 210 carcinomas (CCA), the other 148 cancers were lacking adenomatous features (CSA). CCA occurred more frequently in female patients (p = 0.003). Synchronous adenomas were detected in the resected colon of 19 out 62 CCA and of 24 out 148 CSA (p = 0.04). CCA showed the extent of intraparietal spread (p = 0.001), grade (p = 0.007) and stage (p = 0.004) lower than CSA. These characteristics also appeared statistically related to size of the cancers. The adenomatous tissue within CCA was tubular in 4 cases, tubulo-villous in 34 and villous in 24 cases. The villous histotype was statistically related to the older age of patients (p < 0.0001), larger cancer size (p = 0.01), presence of synchronous adenomas in the resected colon (p = 0.02) and higher histologic grade of the cancer (p < 0.05). Patients with CCA evidenced a higher 5-year survival rate (p = 0.02). Our results evidence epidemiologic, clinical and pathologic differences between CCA and CSA and suggest a possible double histogenesis of colon cancer.

Adenoma↗