Biomedical subjects

G Portella

Publications and source records attributed to G Portella.

At least 37 records · Page 2Linked to original sources

PubMed2000

Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients.

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

Adolescent↗

PubMed1999

[What will jugular bulb oxygen saturation monitoring tell?].

Global cerebral oxygenation can be measured by means of a catheter introduced in the internal jugular vein and placed retrograde in the jugular bulb. The measure of oxygen saturation sampled from the jugular vein (SjvO2) depends on cerebral metabolism and blood flow. This parameter describes the relative balance between oxygen delivery to the brain and oxygen consumption by the brain. SjvO2 remains normal until cerebral blood flow is proportional to cerebral metabolic demands. Any disturbances that increase cerebral metabolism and/or diminishes cerebral oxygen supply determines a reduction of SjvO2. Correspondingly, a decrease of oxygen consumption and/or an increase of oxygen supply may induce an increase of SjvO2. Therefore, SjvO2 is a useful monitor to assess the adequacy of cerebral circulation in patients with neurologic illness, allowing detection of state of hypoperfusion. Monitoring cerebral oximetry in comatose patients is of great importance in order to prevent, detect, control and understand secondary brain insults and damage which are mainly ischemic/hypoxic in nature. Although SjvO2 was shown to be highly sensitive in the presence of global hypoxia or ischemia, the occurrence of focal ischemia may still go undetected. Besides this, elevated SjvO2 should not be universally interpreted as hyperaemia. Instead, the presence of an elevated SjvO2 is a heterogeneous condition. Increased SjvO2 may be alarming prognostic indicators that carry important implications for comatose patients management.

Blood Gas Analysis↗

PubMed1999

Human N-ras, TRK-T1, and RET/PTC3 oncogenes, driven by a thyroglobulin promoter, differently affect the expression of differentiation markers and the proliferation of thyroid epithelial cells.

The ras family members and the tyrosine kinases RET and TRK are frequently activated in human tumors of the thyroid gland. To ascertain the effects of these oncogenes in cultured thyroid cells we have generated expression vectors containing activated versions of the three genes under the control of the thyroid-specific thyroglobulin gene promoter. Here we show that the expression of the three oncogenes differently affects thyroid differentiation. While the TRK-T1 oncogene interferes with the capability of thyroid cells of trapping iodide and only marginally affects thyroglobulin gene expression, both RET/PTC3 and N-ras(Gln61-Lys) induce a dramatic reduction of thyroglobulin mRNA and alleviate TSH dependency for cellular growth. However, none of the three oncogenes is able to induce the appearance of neoplastic transformation markers, such as growth in semisolid medium and tumorigenicity in athymic mice. This indicates that genetic events additional to TRK, RET, or N-ras activation are required for fully malignant transformation of thyroid cells.

Animals↗

PubMed1998

Epithelial carcinogenesis in the mouse: correlating the genetics and the biology.

Tumour formation relies on a complex combination of genetic and environmental factors. In particular, the contributions from inherited predisposition genes as well as carcinogens, for example from cigarettes or in the diet, are amongst the major contributors to tumorigenesis. Since the study of such processes in particularly difficult in human cancers, the availability of a well-defined model system is of obvious benefit. The mouse skin model of multistage carcinogenesis offers an excellent tool for the study of the target cells, the target genes and the biological events associated with neoplasia. In this system, tumorigenesis occurs in a series of defined stages, each of which is characterized by specific and reproducible alterations in genes such as H-ras, cyclin D1, p53 and p16INK4A. Additional changes occur in the production of, or response to, factors such as transforming growth factor beta (TGF beta). These genetic and biological alterations are mirrored in human tumours of epithelial origin. Hence, research into the general principles of tumour initiation, promotion and progression in the context of the mouse skin model is likely to prove valuable in the continual search for new methods for the diagnosis, prevention, and therapeutic treatment of human cancers.

Animals↗

PubMed1998

Jugular saturation (SjvO2) monitoring in subarachnoid hemorrhage (SAH).

Jugular saturation (SjvO2) monitoring was performed in 26 SAH patients to evaluate the incidence of normal (0.56-0.74) and pathological SjvO2 values in this population and to describe its time course in the first 12 days. We also attempt to quantify the influence of systemic and cerebral hemodynamics on SjvO2 and to assess the relationship between cerebral injury volume measured on CT scan and SjvO2. Mean SjvO2 was 0.66 +/- 0.07 (354 samples, median 0.67, range 0.43-0.89). 73% of the observations (259/354) were in the normal range. On serial measurements, we identified only 37/354 (10%) desaturation episodes (D.E.). ICP was significantly higher during low SjvO2 observation (p = 0.008). No statistical differences were noted regarding the influence of MAP, CPP, PaCO2, PaO2 on SjvO2 but during D.E., lower PaCO2 and CPP were more frequently observed. CT scan lesions > 25 ml were associated initially with lower SjvO2 values and with higher values at second CT.

Adult↗

PubMed1998

TPA induces a block of differentiation and increases the susceptibility to neoplastic transformation of a rat thyroid epithelial cell line.

The PC Cl 3 cell line is a well-characterized epithelial cell line of rat thyroid origin. This cell line retains in vitro the typical markers of thyroid differentiation: thyroglobulin (TG) synthesis and secretion, iodide uptake, thyroperoxidase (TPO) expression, and dependency on TSH for growth. Although the differentiated phenotype of thyroid cells has been relatively well described, the molecular mechanisms that regulate both differentiation and neoplastic transformation of thyroid cells still need to be investigated in detail. Protein kinase C (PKC), the target of tetradecanoylphorbol acetate (TPA), regulates growth and differentiation of several cell types. Here we show that treatment of PC Cl 3 cells with TPA induces an acute block of thyroid differentiation. TPA-treated PC Cl 3 cells are unable to trap iodide and the expression levels of thyroglobulin, TSH receptor, and TPO genes are drastically reduced by TPA treatment. This differentiation block is not caused by a reduced expression of one of the master genes of thyroid differentiation, the thyroid transcription factor 1 (TTF-1). TPA-treated PC Cl 3 cells display an increased growth rate indicating that, in addition to the differentiation block, TPA also significantly affects the growth regulation of thyroid cells. Finally, TPA treatment dramatically increases the number of transformation foci induced in PC Cl 3 cells by retroviruses carrying v-Ki-ras, v-Ha-ras, and v-mos oncogenes. These findings support the notion that the PKC pathway can influence proliferation, differentiation, and neoplastic transformation of thyroid cells in culture.

Animals↗

PubMed1998

Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion.

Transforming growth factor beta1 (TGF-beta1) regulates both cell growth and cellular plasticity and is therefore important in the molecular control of both the developmental and neoplastic processes. It has been suggested that TGF-beta1 may be a positive or negative regulator of tumorigenesis. Stimulation of tumorigenesis could be due to its action as an immunosuppressor or as an inducer of angiogenesis, or by its direct action on the cell in promoting cellular plasticity. In the current study, we provide evidence that TGF-beta1 can act directly on keratinocytes in vivo to induce the reversible epithelial-mesenchymal conversion of a malignant metastatic keratinocyte cell line. Two squamous clones from the cell line were shown to undergo a reversible conversion to a fibroblastoid phenotype after culture in 1 ng/ml TGF-beta1. The morphological conversion became apparent at 24 h post-TGF-beta treatment and was complete after another 24 h. The conversion was characterized by a rapid delocalization of E-cadherin within 6-12 h posttreatment, followed by down-regulation of E-cadherin levels by 72 h. These squamous clones spontaneously converted to a fibroblastoid phenotype after s.c. injection in nude mice. Importantly, four of four clones that had been stably transfected with a dominant negative TGF-beta type II receptor were unable to undergo this mesenchymal switch in vivo, despite the fact that all clones stably transfected with neomyocin resistance alone retained their spindle characteristics in vivo. This demonstrates that the epithelial-mesenchymal conversion event is mediated directly via the TGF-beta signaling pathway of the tumor cell per se, and that it is sufficient to significantly enhance tumorigenicity and the malignant and invasive characteristics of the tumor in vivo.

Animals↗

PubMed1998

[Cerebral blood flow in subarachnoid hemorrhage].

Cerebral blood flow (CBF) following subarachnoid haemorrhage varies according to the time of sampling, with regard to the time of bleeding, to clinical conditions of patients and to any possible occurrence of vasospasm. CBF is proportionally reduced upon clinical conditions, involves the totality of patients and represents a diffuse bilateral phenomenon, not dependent on the location of the aneurysm. Following events, such as vasospasm, may deteriorate haemodynamic conditions, especially when unstable. Thus, CBF monitoring is necessary and useful in these patients. The evaluation of this parameter, according to the metabolic demands, appears rather fundamental. Besides, during the first two weeks, all the available therapeutic strategies have to employed in order to achieve the best optimization of the CBF so as to avoid the occurrence or at least minimising the extent of ischemic cerebral lesions.

Cerebrovascular Circulation↗

PubMed1998

[The use of jugular saturation in monitoring patients with subarachnoid hemorrhage ].

We evaluated the usefulness of monitoring jugular saturation (SjO2) in subarachnoid haemorrhage patients. SjO2 is an index of the global ratio between cerebral blood flow and metabolism. Low SjO2 identified global cerebral flow reduction, as due to low cerebral perfusion pressures or hypocapnia, but not regional ischemic phenomena related to vasospasm.

Adult↗

PubMed1996

Development of mammary and cutaneous gland tumors in transgenic mice carrying the RET/PTC1 oncogene.

RET/PTC1 is a chimeric oncogene created by the fusion of the tyrosine kinase domain of RET to the 5'-terminal region of another gene named H4. So far, this oncogene has been found activated only in human papillary thyroid carcinomas. In order to investigate its transforming properties in vivo, we have produced transgenic mice carrying RET/PTC1 under the control of the H4 promoter. The transgene was expressed in several tissues, consistently with the ubiquitous expression of the wild type H4 gene. Mammary adenocarcinomas and, less frequently, hyperplasia of sebaceous glands and rare benign skin tumors, named pilomatrixomas, developed in these mice. The tumors were shown to express the transgene both at the RNA and protein level. These results demonstrate that the transforming ability of the RET/PTC1 oncogene is not restricted to the thyroid epithelium in vivo. Despite its ubiquitous expression, however, RET/PTC1 was able to induce only a limited number of tumor types; specifically mammary epithelium was affected by transgene expression, thus suggesting that RET/PTC1 is able to couple with transforming pathways specific for these glandular cells.

Age Factors↗

PubMed1996

Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice.

Gene rearrangements activating the RET proto-oncogene are frequently associated with human thyroid carcinomas belonging to the papillary subtype. These arrangements cause the fusion of the tyrosine-kinase domain of RET to the 5'-terminal region of different genes creating the RET/PTC chimeric oncogenes. Here we report the generation of transgenic mice lines expressing the RET/PTC1 oncogene under the control of the thyroid-specific rat thyroglobulin promoter. RET/PTC1-transgenic mice developed thyroid tumors displaying the histological aspect of papillary carcinomas. These tumors were slowly progressive and did not cause premature death of the animals. Two additional mice developed areas of thyroid hyperplasia. Immunohistochemical and reverse-transcriptase polymerase chain reaction analyses confirmed the thyroid-specific expression of the transgene. Given the frequency of activating rearrangements of RET in human papillary thyroid carcinomas we conclude that this animal system could be a good model for studying the neoplastic progression of thyroid carcinomas.

Animals↗

PubMed1994

Seminal ribonuclease inhibits tumor growth and reduces the metastatic potential of Lewis lung carcinoma.

The role of some RNases as antitumoral agents has been recently emphasized. We have previously demonstrated a striking inhibitory effect of bovine seminal RNase on the in vitro growth of tumor cells of metastatic origin. This has prompted us to test the effects of this protein in vivo on the induction of metastatic foci in mice lungs after i.m. injection of a highly metastatic Lewis lung carcinoma cell line. The results presented here, while confirming and expanding upon those previously reported on the antitumor effects of bovine seminal RNase in vivo on primary thyroid epithelial tumors, indicate for the first time that bovine seminal RNase can also be regarded as a potent antimetastatic agent on in vivo spontaneous metastases.

Animals↗

PubMed1994

A switch from stromal to tumor cell expression of stromelysin-1 mRNA associated with the conversion of squamous to spindle carcinomas during mouse skin tumor progression.

We previously reported that the expression of stromelysin-1 (ST-1), a matrix-degrading metalloproteinase, correlates with tumor progression in the mouse skin model of carcinogenesis. Using in situ hybridization techniques, we confirmed in this study the expression of ST-1 mRNA in mouse skin keratinocytes treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and also observed dramatic expression of ST-1 message in underlying fibroblastic cells. Benign tumors formed by an initiation/promotion protocol expressed low levels of ST-1 mRNA, which was localized exclusively to stromal tissue surrounding the tumor cells. Squamous cell carcinomas, produced either by chemical carcinogenesis or by injection of cultured cells derived from chemically initiated squamous cell tumors, expressed high levels of ST-1 mRNA, which was also localized to adjacent stromal tissues. In contrast, aggressive, highly metastatic spindle cell tumors expressed ST-1 mRNA in the tumor cells as well as in normal, adjacent stroma. These results suggest that the change from ST-1 expression in surrounding stromal cells to its expression in the tumor cells themselves is associated with the conversion of squamous to spindle carcinomas and may play a causal role in the ability of these cells to invade and metastasize.

Animals↗

PubMed1993

Production of transgenic mice expressing the Ki-ras oncogene under the control of a thyroglobulin promoter.

Transgenic mice have been generated bearing three fusion genes consisting of: (a) a 900-base pair rat thyroglobulin promoter followed by a gene coding for a chloramphenicol acetyl transferase activity; (b) the same promoter followed by the complementary DNA of the human activated Ki-ras oncogene; (c) a 2000-base pair rat thyroglobulin promoter followed by the complementary DNA of the human activated Ki-ras. We have shown that the 900-base pair rat thyroglobulin promoter is able to direct the expression of the reporter gene specifically in the thyroid gland of transgenic mice. The mice bearing the two Ki-ras constructs, which express the transgene in thyroid glands, show thyroid abnormalities, although at very low incidence. These lesions appear after a long latency and with a benign aspect, thus suggest that, in agreement with literature data on naturally occurring human thyroid tumors, the action of an activated ras gene is not sufficient to attain a complete malignant conversion of thyroid glands in vivo. However, ras expression in thyroid follicular cells represents a favorable ground for tumor development, as shown by the fact that goitrogen stimulation experiments increase the occurrence of tumors.

Adenoma↗

PubMed1993

Enhanced response to daunomycin of normal, tumor and metastatic cell lines via drug photoactivation.

We have compared the cytotoxicity of daunomycin in vitro to highly differentiated normal epithelial cells (Fisher rat thyroid cells, FRTL-5) and to two neoplastic cell lines, a thyroid carcinoma (TK-6) and its lung metastasis (MPTK-6). Whereas the cell lines are equally sensitive to the drug in the dark, if irradiated during incubation with daunomycin (86 J/cm2 at 488 nm), they become more and differently sensitive. Namely, the drug doses producing 50% mortality decrease by factors of about 22, 28 and 16 for FRTL-5, TK-6 and MPTK-6 cell lines, respectively. This result correlates with differences in drug uptake and resistance observed in the normal and neoplastic cell lines.

Animals↗

PubMed1992

In vivo and in vitro growth-inhibitory effect of bovine seminal ribonuclease on a system of rat thyroid epithelial transformed cells and tumors.

We investigated the antitumoral effect of bovine seminal RNase (BS-RNase) in vivo and in vitro on a model system of epithelial tumor- and metastasis-derived cells as well as on epithelial tumors derived from the same system. We found that while BS-RNase significantly inhibited the growth in vitro of the epithelial tumor-derived cells, its inhibitory effect was even more dramatic on the growth of metastasis-derived cells. BS-RNase exerted no appreciable growth inhibition on normal thyroid epithelial cells. When administered in vivo to rats bearing solid carcinomas, having the same thyroid origin, BS-RNase induced a drastic reduction in the tumor weight, with no detectable toxic effects on the treated animals. These data show, for the first time on a system of neoplastically transformed epithelial cells, that BS-RNase has a potent specific antitumoral activity.

Animals↗

PubMed1991

NK and LAK susceptibility varies inversely with target cell MHC class I antigen expression in a rat epithelial tumour system.

Several cell clones derived from cell lines obtained from a rat thyroid carcinoma, induced by in vivo injection of the Kirsten murine sarcoma virus into thyroid gland, and from its spontaneous lung metastases were analysed for their major histocompatibility complex (MHC) class I antigen expression. The susceptibility to natural killer (NK) cell lysis of these clones, differing in their levels of MHC class I antigen expression, was determined and found to vary inversely with the target cell MHC level, confirming numerous reports of the literature. We then tried to localize the step of the multistage natural cytotoxic process, in which class I antigens could interfere, and tested first whether lymphokine (IL-2) activation of the killer (LAK) cells could overcome the differences in MHC class I expression of target cells. As this did not appear to be the case, we studied the binding step by either a cold target inhibition assay and a target binding assay and found that target cells expressing class I antigens show a lower competitive capacity for effector cells than targets not expressing such antigens, indicating that this interference may occur, at least in our system, in the binding step of the cytotoxic process.

Animals↗

PubMed1989

Analysis of the HMGI nuclear proteins in mouse neoplastic cells induced by different procedures.

Four malignant tumors induced in mouse by different experimental procedures were compared as regards their high-mobility-group (HMG) proteins. All tumors showed the complete set of three HMG proteins which we call HMGI-C, I-D, and I-E. The presence of the three HMGI proteins is a characteristic of the transformed phenotype regardless of whether the tumor was chemically, virally, or spontaneously derived. However, the level of expression of the HMGI proteins is not constant in the four tumors. Using reverse-phase HPLC, the individual HMGI proteins were isolated from the spontaneously derived tumor (Lewis lung carcinoma) and shown by amino acid analysis to be similar to those previously obtained from a tumor grown in nude mice by inoculation of in vitro-transformed cells.

Amino Acids↗