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Biomedical subjects

A Vacca

Publications and source records attributed to A Vacca.

At least 145 records · Page 8Linked to original sources

Birth by vacuum extraction: neonatal outcome.

Subgaleal (subaponeurotic) haemorrhage (SGH) is a serious and sometimes life-threatening condition associated with vacuum extraction. With increasing use of the vacuum extractor as the preferred instrument for assisted vaginal delivery, neonatal paediatricians should be prepared to encounter a greater number of infants with SGH and other effects associated with vacuum extraction. In order to reduce morbidity and to prevent mortality in infants with SGH, neonatal caregivers should be able to recognize the occurrence of this type of bleeding and to institute appropriate forms of management. This annotation describes the effects of vacuum extraction on the newborn infant and suggests some measures for the management of these conditions.

Female↗

Expression of tenascin is related to histologic malignancy and angiogenesis in b-cell non-Hodgkin's lymphomas.

The topography of and the area covered by tenascin, laminin and type IV collagen (all components of the subendothelial basement membrane), and the microvessel area (an index of angiogenesis), as evaluated with factor VIII, were investigated immunohistochemically in 61 B-cell non-Hodgkin's lymphomas (B-NHL) and 30 benign lymphadenopathies as controls. The three components were located in the microvessels and in a microvessel-bound stromal reticular network, the expression of tenascin being always more extended and finer than the other components. Of the lymphadenopathies, reactive and atypical lymphoid hyperplasias showed vessels and stromal network in the interfollicular zone only, whereas in Castleman's and angioimmunoblastic forms these structures were widely scattered in the tissue, and the area of the three components and that of the microvessels were significantly larger. Of the low-grade B-NHL, follicular subtypes had vessels and stromal network confined to the interfollicular inflammatory zone, but not in tumor follicles, whereas these structures were irregularly distributed throughout the small lymphocytic subtype. The levels of areas in low-grade B-NHL overlapped those of Castleman's and angioimmunoblastic lymphadenopathies. Among the intermediate-grade tumors, the follicular subtype resembled the follicular tumors, and the diffuse subtypes displayed vessels and stromal network throughout the tissue in close association with the neoplastic cells, and with significant increments of both the tenascin and the microvessel areas, but with a significant reduction of both the laminin and the type IV collagen areas. Distribution was similar in high-grade B-NHL, but tenascin and microvessel area variations, on the one hand, and those of laminin and type IV collagen areas were still more apparent than in the intermediate-grade. A high correlation was demonstrated in all groups of tissues between tenascin and microvessel area. In addition, in the diffuse intermediate-grade and high-grade B-NHL highly immature vessels were frequently detected by ultramicroscopy. The results show that tenascin expression and angiogenesis are closely related, and that both increase in function of tumor malignancy. Unlike laminin and type IV collagen, tenascin is associated with highly immature vessels in B-NHL. We suggest that tenascin expression and angiogenesis are governed by the B-NHL-associated inflammatory infiltrate, as well as by the B-NHL cells, particularly in more malignant tumors.

Endothelium, Vascular↗

Fibronectin as a predictor of preeclampsia: a pilot study.

The measurement of serum fibronectin levels in women carrying a singleton pregnancy at between 25-30 weeks' gestation has allowed the separation of those women who will remain normotensive from those who develop preeclampsia in this pilot study. The fibronectin assays were performed using nephelometry. It is recognized that some severe cases of preeclampsia will have already declared themselves clinically by 28 weeks' gestation, but if a screening test is to be limited by cost to a single test event, then this pilot study suggests the 28-week gestation time to be the most suitable. Further studies are being undertaken to test this hypothesis and to adequately assess the test's reliability, predictability and its cost-effectiveness.

Adolescent↗

Basic fibroblast growth factor overexpression in endothelial cells: an autocrine mechanism for angiogenesis and angioproliferative diseases.

Basic fibroblast growth factor (bFGF) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases. The ultimate significance of this observation is poorly understood. We have investigated the biological consequences of endothelial cell activation by endogenous bFGF in a mouse aortic endothelial cell line stably transfected with a retroviral expression vector harboring a human bFGF cDNA. Selected clones expressing M(r) 24,000, M(r) 22,000, and/or M(r) 18,000 bFGF isoforms were characterized by a transformed morphology and an increased saturation density. bFGF transfectants showed invasive behavior and sprouting activity in three-dimensional fibrin gels and formed a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on laminin-rich basement membrane matrix (Matrigel). The invasive and morphogenetic behavior was prevented by anti-bFGF antibody, revealing the autocrine modality of the process. The biological consequences of this autocrine activation were investigated in vivo. bFGF-transfected cells gave rise to highly vascularized lesions resembling Kaposi's sarcoma when injected in nude mice and induced angiogenesis in avascular rabbit cornea. When injected into the allantoic sac of the chick embryo, they caused an increase in vascular density and formation of hemangiomas in the chorioallantoic membrane. In conclusion, bFGF-overexpressing endothelial cells acquired an angiogenic phenotype and recruit quiescent endothelium originating angioproliferative lesions in vivo. These findings demonstrate that bFGF overexpression exerts an autocrine role for endothelial cells and support the notion that tumor neovascularization and angioproliferative diseases can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).

3T3 Cells↗

The chick embryo chorioallantoic membrane as a model for in vivo research on angiogenesis.

The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane that is commonly used in vivo to study both new vessel formation and its inhibition in response to tissues, cells, or soluble factors. Quantitative or semiquantitative methods may be used to evaluate the amount of angiogenesis and anti-angiogenesis. Thanks to the CAM system, angiogenesis could be investigated in association with normal, inflammatory and tumor tissues, and soluble factors inducing angiogenic or anti-angiogenic effects could be identified. Rabbit cornea provides an alternative in vivo system, but CAM appears to be easier to handle and less expensive. Moreover, CAM can be used with very few limitations.

Allantois↗

Nuclear magnetic resonance as a tool for determining protonation constants of natural polyprotic bases in solution.

The acid-base properties of the tetramine 1,5,10,14-tetraazatetradecane H2N(CH2)3NH(CH2)4NH(CH2)3NH2 (spermine) in deuterated water have been studied at 40 degrees C at various pD values by means of NMR spectroscopy. Both one-dimensional 13C[1H] spectra and two-dimensional 1H/13C heterocorrelation spectra with inverse detection have been recorded. A calculation procedure of general validity has been developed to unravel the effect of rapid exchange between the various species in equilibrium as a function of pD of the solution. The method of calculation used in this part of the new computer program, HYPNMR, is independent of the equilibrium model. HYPNMR has been used to obtain the basicity constants of spermine with respect to the D+ cation at 40 degrees C. Calculations have been performed using either 13C[1H] or 1H/13C data individually, or using both sets of data simultaneously. The results of the latter calculations were practically the same as the results obtained with the single data sets; the calculated errors on the refined parameters were a little smaller. After appropriate empirical corrections for temperature effects and for the presence of D+ in contrast to H+, the calculated constants are compared with spermine protonation constants which have been determined previously both from potentiometric and NMR data.

Carbon Isotopes↗

Bone marrow of patients with active multiple myeloma: angiogenesis and plasma cell adhesion molecules LFA-1, VLA-4, LAM-1, and CD44.

Bone marrow plasma cells and stromal cells in multiple myeloma (MM) have been shown to be capable of releasing cytokines with angiogenic properties. Plasma cells can also express adhesion molecules controlling their adhesive interactions with endothelial cells. In the present study, we have evaluated by immunohistochemistry the extent of angiogenesis in the bone marrow of: a) 51 patients with active and non-active MM; b) 25 patients with monoclonal gammopathy of undetermined significance (MGUS). Plasma cells were investigated by flow cytometry for the expression of the adhesion molecules LFA-1, VLA-4, LAM-1, and CD44. The results showed that, while angiogenesis was very low or absent in patients with MGUS and non-active MM, it increased markedly in those with active MM. The highest detectability of plasma cell adhesion molecules, except LAM-1, was also found in these patients. The functional significance of these findings is unknown. Their consistent occurrence in the bone marrow of active myeloma patients, however, strongly suggests that more frequent adhesive interactions between plasma cells and their microvasculature underlie tumor dissemination.

Bone Marrow↗

Androgenic and antiandrogenic control on epidermal growth factor, epidermal growth factor receptor, and androgen receptor expression in human prostate cancer cell line LNCaP.

Both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor (AR). We studied the modification of the expression of epidermal growth factor (EGF), of its receptor (EGF-R), and of androgen receptor (AR) in the LNCaP cell line, under basal conditions and during androgen (R1881) and antiandrogen hydroxy-flutamide (OH-FLU) treatment. After prolonged R1881 administration, a marked increase of EGF release was observed, completely blocked by the addition of OH-FLU. The Scatchard plot analysis of EGF-R binding revealed two classes of binding sites with high and low affinity. The administration of OH-FLU alone or combined with R1881 did not modify the affinity constants, while the low-affinity component disappeared after androgen administration. Both androgen and antiandrogen administration led to a significant increase of the EGF-R high-affinity component. AR mRNA and protein levels were downregulated by R1881 treatment. Following OH-FLU administration, AR mRNA was slightly downregulated, and there was not a strict parallelism between AR mRNA levels and AR binding capacity. When combined with R1881, OH-FLU partially counteracted the androgen-induced AR downregulation. Our data show that EGF-R binding capacity is the only parameter constantly raised in cell proliferation with respect to quiescent cells, and highlights the nonunivocal action of OH-FLU on androgen-induced effects.

Androgen Antagonists↗

Analysis of N-ras mutations in human cutaneous melanoma: tumor heterogeneity detected by polymerase chain reaction/single-stranded conformation polymorphism analysis.

Determination of the activation state of oncogenes as well as tumor suppressor genes is a main subject of interest in the analysis of the mechanism of tumor initiation. In human melanoma, the c-myc and N-ras oncogenes have been found to be activated in approximately 50% and 15% of the analyzed material, respectively. These studies have mostly been done on fresh tumor material or cell lines. Only in a few cases has an attempt been made to look at tumor heterogeneity or clonality with respect to the activation of oncogenes. We have adjusted the polymerase chain reaction (PCR)/single-stranded conformation polymorphism analysis (SSCP) technique to screen paraffin-embedded melanoma material for the presence of N-ras mutations and found genetic defects at particular progression stages. In one melanoma of the skin, we were able to sublocalize an N-ras mutation in the intraepidermal tumor part, that was absent in the part deeply invading the dermal layer. We conclude that a thorough investigation of N-ras activation in human melanoma should include analysis of histologically different parts of the tumor.

Base Sequence↗

Long-term therapy with recombinant human erythropoietin (rHu-EPO) in progressing multiple myeloma.

Recombinant human erythropoietin (rHu-EPO) is an effective growth factor for erythroid progenitor cells in anemia provoked by several conditions, including bone marrow tumors such as multiple myeloma (MM). We studied a group of 54 patients with MM undergoing second-induction chemotherapy. Thirty of them were randomly assigned to receive rHu-EPO at an initial dosage of 150 units/kg body weight three times a week, increased to 300 units/kg from the sixth week to the end of the 24-week study. Hemoglobin (Hb) levels increased in 77.7% of these patients by the eighth week. In addition, five transfusion-dependent patients in treatment with the VMCP protocol completed the trial without requiring blood supplement after the third month, whereas seven control patients required frequent supplements. Monthly assessment of hematologic parameters demonstrated the ability of rHu-EPO to increase reticulocyte counts, whereas five patients became resistant to the second-induction chemotherapy in apparent concurrence with their rHu-EPO therapy. The response to rHu-EPO in four of the five MM patients receiving cytotoxic protocols combined with alpha-interferon (alpha-IFN) included an increase of serum IgM after the third month. This effect was not demonstrable in any other group, including three rHu-EPO-untreated patients undergoing alpha-IFN + VMCP combined therapy, as well as rHu-EPO-treated patients not receiving alpha-IFN. Our data suggest that alpha-IFN plus rHu-EPO treatment in MM patients is effective in restoring normal B cell function. These results may reflect in vivo the modulation of normal human B cells and lymphoblasts by rHu-EPO observed in vitro.

Anemia↗

Immunomodulation of T and B cell functions in multiple myeloma patients treated with combined erythropoietin and alpha-interferon therapy.

T and B lymphocyte functions were investigated in the course of a long-term trial of recombinant human erythropoietin in patients with progressing multiple myeloma. Peripheral mononuclear cell as well as T and B lymphocyte cultures were established at the 1st, 13th, and last week of the 24-week protocol from 16 treated and 15 untreated patients. Control cultures from healthy individuals were also obtained. A suppression of phytohemagglutinin-induced proliferation of T cells was noted in all 1st-week cultures, whereas a variable increase of 3H-thymidine uptake was noted at the end of the trial in the cultures from erythropoietin-treated patients. A significant increase was observed, however, in cultures from 5 erythropoietin-treated patients who also received alpha-interferon when their cells were grown in the presence of the hormone. In contrast, the pokeweed mitogen-driven in vitro synthesis of immunoglobulins was not significantly influenced by the duration of erythropoietin treatment, nor by addition of the hormone. IgG secretion by Epstein-Barr virus-transformed B cells in cultures from 9 erythropoietin-treated and 6 untreated patients was enhanced in the presence of both recombinant human erythropoietin and alpha-interferon. These data suggest that synergy between the two cytokines may variably modulate certain immune functions in vitro. This effect might account for the increase of serum IgM levels noted in some patients who received alpha-interferon.

B-Lymphocytes↗

Gene methylation of oestrogen and epidermal growth factor receptors in neoplastic and perineoplastic breast tissues.

Oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) gene methylation was evaluated in neoplastic and perineoplastic breast tissues from 20 patients. In both tissues, ER gene methylation was inversely correlated with protein levels, while EGFR gene methylation was not. A preferential ER gene hypomethylation was found in neoplastic tissues, suggesting a significant role in neoplastic transformation.

Breast Neoplasms↗

HLA antigen distribution in different clinical subgroups demonstrates genetic heterogeneity in lichen planus.

HLA-A, B, Cw, DR and DQ antigens were serologically determined in 105 patients suffering from lichen planus (LP). Of these patients, 87 had idiopathic LP and 18 had secondary LP. In the first group, 43 had cutaneous LP without mucosal lesions, 17 had cutaneous LP with mucosal lesions and 27 had purely mucosal LP. No HLA antigen was found to be significantly associated with secondary LP or with mucosal idiopathic LP. In cutaneous idiopathic LP with or without mucosal lesions, the HLA-DR1 and DQ1 antigen frequency was significantly increased, and that of HLA-DQ3 significantly decreased. Among the HLA-DR1 cutaneous idiopathic LP patients, 78.5% carried the DRB1*0101 allele, and 21.4% the DRB1*0102 allele, compared with 35.7 and 67.8%, respectively, of the HLA-DR1 controls. Our data demonstrate that idiopathic LP is influenced by HLA-associated genetic susceptibility and resistance factors not involved in secondary LP, and that cutaneous idiopathic LP is a genetically and therefore pathogenetically different condition from purely mucosal idiopathic LP.

Adult↗

Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical studies.

Angiogenesis is a necessary step in solid tumor progression (growth, invasion and metastasis) with which it correlates and is indicative of an unfavourable prognosis. We observed bone marrow angiogenesis in patients with active multiple myeloma (MM), though not in patients with non-active MM nor with monoclonal gammopathies of undetermined significance (MGUS). Microvessel density increased in parallel with the labeling index (LI%)--an indicator of plasma cell proliferating activity that correlates with prognosis--and defined a risk of MM progression in much the same way as LI% itself. Consequently, bone marrow angiogenesis could be an indication for unfavourable prognosis in MGUS and MM. Angiogenesis has also been demonstrated in lymph nodes involved by B cell non Hodgkin's lymphoma (B-NHL) belonging to the Working Formulation intermediate-grade (diffuse subtypes), and high-grade categories, but not in the low-grade and intermediate-grade (follicular subtype) categories. It correlated with the B-NHL cell proliferating activity, since large increments in this activity have already been demonstrated in intermediate- and high-grade vs low-grade tumors. Active MM, intermediate-grade, diffuse subtypes, and high-grade B-NHLs correspond to the vascular phases of B cell lymphoproliferative diseases, and could thus be assimilated to locally invasive and metastatic solid tumors. Similarly to solid tumors during these stages of progression, tumor B cells are also capable of inducing angiogenesis, both directly and indirectly by activating the inflammation infiltrate--a possibility that was first demonstrated by means of B-NHL implants onto the chick embryo chorioallantoic membrane. Anti-angiogenic therapy can be envisaged as a possible future development.

Bone Marrow↗

[Critical course of a case of idiopathic pulmonary fibrosis].

The authors present a case of idiopathic pulmonary fibrosis with an unusual onset in the form of acute interstitial pneumonia. On being admitted to hospital the 53-year-old woman presented an altered breathing pattern which initially required oxygen therapy using Venturi's oxygen mask followed by sedation and mechanical ventilation with appropriate FiO2 to guarantee adequate pO2 and arterial saturation. For diagnostic purposes bronchiolar and alveolar lavage was immediately performed together with transbronchial biopsy during the course of fibrobronchoscopy. The results of these tests revealed a syndrome of interstitial pneumonia and widespread alveolar lesion with an enhanced lymphocyte population. Antibac-terial and immunosuppressive therapy (6-methylprednisolone and cyclophosphamide) commenced on the basis of these tests caused a temporary improvement in blood-gas parameters and parenchymal thickening. But in spite of treatment the patient's cardiocirculatory and respiratory conditions deteriorated, causing death. This case report raises a number of different questions regarding both diagnosis and treatment. With regard to diagnosis it is worth underlining the absence of hyaline membrane, pathognomonic of widespread alveolar lesions, in biopsies removed while the patient was still alive. With regard to treatment, in addition to specific antibiotic and immunosuppressive therapy, the authors consider that surfactants might be of some help given that widespread alveolar damage can be attributed to pulmonary fibrosis.

Female↗

Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif.

Interference with T cell activation signals by Human immunodeficiency virus (HIV) gene products is suggested to contribute to the impairment of immune functions observed in AIDS. Interleukin-2 (IL-2) and HIV share common stimulatory signals triggered during T cell activation. The role of HIV tat, which is the main enhancing factor for viral LTR, in the regulation of IL-2 gene transcription has been studied following transient expression of the tat gene in phorbol ester and calcium ionophore-activated Jurkat cells transfected with IL-2 promoter-chloramphenicol acetyltransferase reporter constructs. We observed that tat increased the IL-2 promoter transcriptional activity in response to phorbol ester and ionomycin. This tat-dependent synergism mapped to the (-279 to -263 bp) NFAT motif of the IL-2 enhancer, which was sufficient to be transactivated by tat. Our data suggest that tat links T cell activating signals to the shared IL-2 and HIV regulation. This may play a role in the early phase of HIV infection.

Calcium↗

Positive and negative regulation of the composite octamer motif of the interleukin 2 enhancer by AP-1, Oct-2, and retinoic acid receptor.

The differentiating agent retinoic acid (RA) has been previously reported to interfere with 12-O-tetradecanoyl-phorbol-13-acetate (TPA)/Ca2+-induced signals for the regulation of the -96 to -66-bp octamer motif found in the enhancer for the interleukin (IL)-2 gene, which encodes a major T lymphocyte growth factor. The IL-2 octamer motif is a composite cis-element which binds Oct-1 and Oct-2 as well as a TPA/Ca2+-inducible nuclear factor, previously termed octamer-associated protein (OAP40). We show here that Oct-2, despite the presence of an active transcriptional activation domain, requires TPA/Ca2+-induced signals to strongly transactivate the IL-2 octamer motif in Jurkat T cells. This Oct-2-dependent transactivation is inhibited by RA. The presence of an intact COOH-terminal domain of Oct-2 contributes to both TPA/Ca2+-induced transactivation and the RA-mediated repression. We also show that both Fos and Jun components of the AP-1 factors participate in the OAP40 complex. Furthermore, transfected c-jun, jun-B, jun-D, c-fos, or Fos-B expression vectors partially substitute for TPA and Ca2+ and cooperate with Oct-2 for the transactivation of the combined OAP/octamer cis-element. Mutations of the genuine octamer-binding site abrogate both the binding of Oct-1 and Oct-2 and the TPA/Ca2+-induced transactivation of the OAP/octamer motif. OAP confers to Oct-2 responsivity to both TPA/Ca2+ and RA, since specific mutations of the AP-1/OAP-binding site significantly reduce the transactivation by Oct-2 in response to TPA and Ca2+ and abolish the inhibition by RA. Furthermore, retinoic acid receptor (RAR) alpha is able to inhibit in vitro the formation of the complex between the nuclear AP-1/OAP and its specific binding site, resulting in the interference with Oct-2-dependent cis-regulatory function of this AP-1 element. Therefore, we propose that the TPA/calcium-activated AP-1/OAP element is the main target of positive or negative regulatory signals influencing the IL-2 octamer motif, through synergism with Oct-2 and antagonism by RAR.

Base Sequence↗