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R Bianchi

Publications and source records attributed to R Bianchi.

At least 181 records · Page 10Linked to original sources
PubMed1992

Immunocytochemical localization of annexin V (CaBP33), a Ca(2+)-dependent phospholipid- and membrane-binding protein, in the rat nervous system and skeletal muscles and in the porcine heart.

We investigated the ultrastructural localization of annexin V a Ca(2+)-dependent phospholipid- and membrane-binding protein in the nervous system, heart, and skeletal muscles. The results indicate that in the cerebellum the protein is restricted to glial cells, where it is found diffusely in the cytoplasm as well as associated with plasma membranes. Bergmann glial cell bodies and processes and astrocytes in the cerebellar cortex and oligodendrocytes in the cerebellar white matter displayed an intense immune reaction product. In sciatic nerves, the protein was exclusively found in Schwann cells with a subcellular localization similar to that seen in glial cells in the cerebellum. Pituicytes in the neurohypophysis were intensely immunostained, whereas axons were not. In the heart, annexin V was restricted to the sarcolemma, transverse tubules, and intercalated discs. In skeletal muscles the protein was localized to the sarcolemma and transverse tubules. No evidence for the presence of the protein in the sarcoplasm or in association with mitochondria, the sarcoplasmic reticulum, or contractile elements was obtained. The observation that plasma membranes in cells expressing annexin V have the protein associated with them is in agreement with previous data on Ca(2+)-dependent binding of the protein to brain and heart membranes, and on existence of both EGTA- and Triton X-100-extractable and resistant fractions of annexin V in these membranes. The present data support the hypothesis that annexin V might be involved in membrane trafficking and suggest a role for this protein in the regulation of cytoplasmic activities in glial cells.

Animals↗
PubMed1992

O6-methylguanine-DNA methyltransferase activity and induction of novel immunogenicity in murine tumor cells treated with methylating agents.

To investigate the mechanism of the generation of immunogenic tumor variants by mutagenic drugs, murine leukemia cells exhibiting different sensitivity to killing by the alkylator 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and different ability to repair O6-methyl-guanine in their DNA were treated in vitro with a series of methylating agents, including triazene derivatives, temozolomide, and streptozotocin. At the population level, we found that BCNU-resistant cells (L1210/BCNU) that appeared to be cross-resistant to killing by a dimethyltriazene and expressed high levels of O6-methylguanine-DNA methyltransferase activity (mer+ phenotype) failed to generate highly immunogenic variant sublines on repeated exposure to the methylating agents. In contrast, all cells (L1210) that were susceptible to DNA alkylation damage and deficient in O6-methylguanine repair (mer-) developed immunogenic variant sublines. A noticeable exception was represented by streptozotocin treatment, which was equally effective in mer+ and mer- cells. At the clonal level, a single exposure to streptozotocin or a triazene derivative resulted in a high incidence (33% and 50%, respectively) of immunogenic cell generation in mer- cells only. In mer+ cells, streptozotocin treatment led to a 33% incidence of immunogenic clones only when the cells were concurrently exposed to O6-methylguanine as a free base. The activity of O6-methylguanine-DNA methyltransferase in mer+ cells was greatly reduced by treatment with O6-methylguanine or streptozotocin, and the combination of the two drugs led to enzyme levels similar to those observed in mer- cells. Taken together, these data suggest that the mechanism of O6-alkylation may be operative in the induction of novel tumor-cell antigenicity by methylating agents.

Alkylating Agents↗
PubMed1992

Specific effects of the benzodiazepine midazolam on visual receptive fields in light and dark adapted human subjects.

Psychophysical experiments in humans have revealed similar characteristics of visual receptive fields as were found in cats and monkeys from retinal ganglion cell recordings. In addition, in some retinal ganglion cells of cats the GABA antagonist bicuculline decreases the activity of the inhibitory surround. These findings led to two predicitions: 1) benzodiazepines will selectively increase the inhibitory surround of human visual receptive fields, 2) after dark adaptation, no free GABA will be available in the synapses and benzodiazepines will have no effect on the visual system. Characteristics of human receptive fields were determined by subthreshold summation: the contrast threshold of a vertical line was measured dependent on the distance of two parallel flanking lines whose contrast was below threshold. Both hypotheses were confirmed: the threshold in the inhibitory region of receptive fields was specifically increased in a dose-dependent manner by midazolam PO (7.5 mg: P < 0.05; 15 mg: P < 0.01). In dark-adapted subjects no effect of midazolam was found. Control experiments with atropine (1 mg IV), sulpiride (100 mg IM), and levodopa (100 mg PO) showed no specific effect. The visual system may be a model to bridge the gap between animal and human psychopharmacology.

Adaptation, Ocular↗
PubMed1992

The concomitant determination of different tumor markers in patients with epithelial ovarian cancer and benign ovarian masses: relevance for differential diagnosis.

The serum levels of CA 125 (cutoff limit, 65 U/ml), CA19.9 (cutoff, 40 U/ml), CA 15.3 (cutoff, 32 U/ml), CA72.4 (cutoff, 3.8 U/ml), and TATI (cutoff, 22 ng/ml) were preoperatively measured in 90 patients with epithelial ovarian cancer and in 254 patients with benign ovarian pathology. CA125 had a sensitivity of 75.6%, a specificity of 86.6%, and a diagnostic accuracy of 83.7% for epithelial ovarian cancer; CA19.9 had a sensitivity of 35.6%, a specificity of 81.1%, and a diagnostic accuracy of 69.2%; CA15.3 had a sensitivity of 57.1%, a specificity of 93.9%, and a diagnostic accuracy of 84.6%; CA72.4 had a sensitivity of 70.7%, a specificity of 91.8%, and a diagnostic accuracy of 86.2%; and TATI had a sensitivity of 47.3%, a specificity of 95.3%, and a diagnostic accuracy of 82.9%. CA 125 was the most sensitive marker for nonmucinous tumors, while CA19.9 and CA72.4 were the antigens more frequently expressed by mucinous malignancies. The sensitivities of serum CA 125 (81.1% vs 50.0%; P = 0.01) and TATI (55.2% vs 18.8%; P = 0.02) were higher in patients above 50 years of age than in younger patients while specificities were quite similar in both age groups. The association of serum CA125 and CA19.9 had a significantly higher sensitivity (93.2% vs 81.1%; P = 0.03) and a slightly lowered specificity (78.9% vs 86.0%; P = 0.46) than CA125 assay alone in the differential diagnosis of ovarian masses in patients above 50 years of age.

Adenocarcinoma↗
PubMed1992

The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients.

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Tumor-specific L3T4+ and Lyt-2+ lymphocytes in mice primed to mutagenized cell variants.

We have investigated the tumor-specific reactivity of different T-cell subsets from mice primed with clonal variants of L5178Y and P815 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both tumor systems, anti-parental tumor immunity and protection against non-immunogenic clones were only induced by vaccinating the hosts with highly immunogenic cell variants, and the effect correlated with the detection of TATA-specific delayed-type hypersensitivity (DTH) reactions. The footpad reaction was transferable with spleen cell populations from immunized mice, and enrichment of splenic lymphocytes in L3T4+ but not Lyt-2+ lymphocytes increased the footpad swelling. Unfractionated spleen cell populations from immunized mice released high amounts of IL-2 and IFN-gamma in vitro in response to parental antigens. Purified L3T4+ and Lyt-2+ lymphocytes also produced IFN-gamma when incubated in vitro with the parental tumors and accessory cells. It is suggested that the mechanisms of anti-parental tumor immunity induced by MNNG-treated variants may be similar to those described previously for triazene-xenogenized L5178Y/DTIC cells, and may involve induction of a tumor-specific DTH reaction and IFN-gamma-mediated stimulation of non-specific tumoricidal effects.

Animals↗
PubMed1992

Experimental studies of immunotoxicity of a photosensitizing agent (Photofrin II) in mice.

Immunotoxicity studies have been performed on the photosensitizing agent Photofrin II (PHFR), a porphyrin derivative used in photodynamic therapy. Hybrid CD2F1 (H-2d/H-2d) or inbred C57Bl/6 (H-2b) male mice were injected with graded doses of the agent (from 1.2 to 12 mg/Kg ip) on day -5, -3 and -1 before assays. The animals, or spleen cells collected from them on day 0 with respect to PHFR treatment, were tested for: a) competence of producing GVHD upon cell transfer into allogeneic, immunosuppressed recipients; b) graft response against challenge with allogeneic lymphoma cells; c) delayed-type hypersensitivity (DTH) against sheep red blood cells; d) in vitro response to mitogens; e) NK cell activity; f) in vitro generation of alloreactive cytotoxic T lymphocytes (CTL); g) resistance against the challenge of a sublethal dose of Pseudomonas aeruginosa. Moreover the LD50 of the drug given ip has been determined in male CD2F1 mice. The results show that PHFR, even at the highest doses used, does not affect most of the immunological parameters studied, except for a marginal inhibition of CTL generation and increment in proliferative responses to Con A or LPS. These data along with parallel studies performed by our group on human models in vitro, showing increased susceptibility of PHFR-treated tumors to NK or LAK effector cells, point out that PHFR, in the absence of systemic photoactivation, is essentially non-immunotoxic in vivo and could render tumor cells more susceptible to natural immunity.

Animals↗
PubMed1992

Intrinsic organization of the paramedian pontine reticular formation of the cat.

A morphoquantitative analysis was carried out to clarify the cytoarchitectural organization of the paramedian pontine reticular formation (PPRF) which is considered to be an important site in the control of eye movements. The study was carried out on the cat, using the Golgi staining method. The topographic position and detailed structure of the neurons were demonstrated using morphoquantitative methods. On the basis of their neuronal arborization, fusiform neurons and two types of multipolar cells were identified. Fusiform neurons show dendrites which are given off from the two poles of the small- to medium-sized cell body. The arborization generally runs caudorostrally, ending inside the PPRF. These neurons are ubiquitous. Type 1 multipolar neurons, the most frequent elements of the neuronal population (60%), have a small- to large-sized cell body from which 2 or 3 primary spiny dendrites and the axon emerge. Their dendritic field is oval and generally oriented in the vertical plane. These neurons are scattered everywhere in the PPRF. Type 2 multipolar cells are large neurons endowed with numerous primary spiny dendrites constituting a wide round dendritic field and with a thick axon. They are located almost exclusively at the boundaries of the PPRF and preferentially in the caudal region. The characteristics of the neurons suggest that the fusiform cells may play an interneuronal role, while the multipolar neurons could have both a projective function and an important receptive role for the afferent fibers to the PPRF. The lack of homogeneity found among the multipolar neurons is in agreement with the variety of projective elements shown by functional investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Combined evaluation of serum CA 125 and CAM 29 in patients with epithelial ovarian cancer.

We examined 92 patients with epithelial ovarian cancer and 262 patients with benign ovarian diseases undergoing laparotomy. On the basis of a nonparametric method, antigen levels corresponding to prefixed 95% specificity values in a group of 674 women with benign gynecologic diseases were taken as cutoff limits (88.8 U/ml for CA 125 and 13.7 U/ml for CAM 29). Moreover, CA 125 and CAM 29 levels were measured serially during and after chemotherapy in 26 women selected from the patients with advanced epithelial ovarian cancer. At diagnosis, serum CA 125 was as sensitive as serum CAM 29 for nonmucinous tumors, but more sensitive than serum CAM 29 for mucinous tumors. The association of the two markers seemed to give no advantage over the CA 125 assay alone in the diagnosis of epithelial ovarian cancer. In monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer, changes in CA 125 levels correlated with the clinical course of disease better than changes in CAM 29 levels, and the serum CA 125 assay was more reliable than the serum CAM 29 assay in the early detection of tumor progression. In conclusion, serum CAM 29 did not seem to represent a complementary assay to serum CA 125 in the management of patients with epithelial ovarian cancer.

Adolescent↗
PubMed1991

'Neuron-specific' protein gene product 9.5 (PGP 9.5) is also expressed in glioma cell lines and its expression depends on cellular growth state.

Protein gene product 9.5 (PGP 9.5), which in the normal nervous system is restricted to certain neurons, has been detected in two glioma cell lines, rat C6 and human GL15, by immunoblotting and immunocytochemistry. Its expression in these cells depends on the cellular growth state, being maximal between the first and second post-plating day. Only a faint PGP 9.5 immunoreactivity can be observed in glioma cells after the eleventh post-plating day, i.e. about one week after confluency has been reached. The present results suggest that PGP 9.5 in cultured glial cells is maximally expressed during the growth phase and that the protein could play a role during brain development in glial cells, in reactive gliosis, or in tumorigenesis of the glial lineage.

Amino Acid Sequence↗
PubMed1991

Inner ester derivatives of gangliosides protect autonomic nerves of alloxan-diabetic rats against Na+, K(+)-ATPase activity defects.

Bovine brain gangliosides have been shown to prevent decay in Na+,K(+)-ATPase activity in sciatic and optic nerves of alloxan- and streptozotocin-diabetic rats. In the search for a drug with greater bioavailability and increased incorporation into neural tissue, ganglioside inner ester derivatives (AGF1) were recently developed. We evaluated the effect of AGF1 treatment on Na+,K(+)-ATPase activity in homogenates of vagus nerve from alloxan-diabetic rats (100 mg/kg s.c.). Animals were treated with AGF1: 10 mg/kg 6 days/week i.p., or 30 mg/kg biweekly i.p. Treatment began 10 d post-alloxan and continued for 8 consecutive weeks. Normal age- and sex-matched rats were used as controls. Alloxan intoxication produced a 39% decrease in Na+,K(+)-ATPase activity of the vagus nerve, which was completely restored (96-97% recovery) by both AGF1 regimes. Results suggest that ganglioside inner ester derivatives may be used in the clinical setting for the management of diabetic autonomic neuropathy.

Animals↗
PubMed1991

Immunohistochemical localization of annexin V (CaBP33) in rat organs.

We investigated the cellular distribution of annexin V (CaBP33) in rat tissues by immunohistochemistry. Several cell types were shown to express the protein. Glial cells in the cerebellum and in the optic nerve, the corneal epithelium, the posterior epithelium in the iris, chondrocytes, skeletal muscle cells and cardiomyocytes, the capillary endothelial cells in many organs, the muscularis mucosae and the muscular layer in the intestinal tract, hepatocytes, Müller cells in the retina, the lens fibers, Sertoli and Leydig cells in the testis, and smooth muscle cells in the epididymis and bronchi displayed intense immunostaining. In the adrenal gland, only the cortex showed immunoreaction product. In the kidney, no apparent staining of renal cells was observed, whereas endothelial cells of peritubular capillaries were stained. In the heart, annexin V was found associated exclusively with the sarcolemma and intercalated discs, as opposed to the diffuse distribution of the protein in skeletal muscle cells. In the spleen, only reticular elements in the white pulp and endothelial cells in the red pulp appeared to be immunostained. The present data complement the biochemical work thus far done on annexin V and suggest that the protein is neither restricted to secretory cells nor exclusively related to exocytotic events in secretory cells.

Animals↗
PubMed1991

Comparison of tumor-associated trypsin inhibitor (TATI) with CA125 as a marker for diagnosis and monitoring of epithelial ovarian cancer.

Preoperative serum levels of CA125 and tumor-associated trypsin inhibitor (TATI) were measured in 220 patients undergoing laparotomy for adnexal masses. Of the 57 patients with epithelial ovarian cancer. 86% had serum CA125 higher than 35 kU/l and 81% higher than 65 kU/l while 51% had serum TATI above 22 micrograms/l. In eight patients with mucinous ovarian malignancies, serum levels of CA125 were above 65 kU/l in 6 cases while serum TATI was above 22 micrograms/l in 4 cases. Of the 163 patients with benign ovarian masses, 41% had serum CA125 levels above 65 kU/l and 17% above 65 kU/l whereas serum TATI was above 22 micrograms/l in 6%. In 11 cancer patients having elevated levels of both CA125 and TATI at diagnosis, the serum concentrations of these antigens were periodically measured during and after treatment. Changes in CA125 and TATI levels correlated with the clinical course in 84% and 37% of the instances, respectively. After the sixth course of chemotherapy, the diagnostic accuracy of the markers in the evaluation of the disease status at second-look laparotomy was 55% for CA125 with a cut-off level of 35 kU/l, 36% for a cut-off level of 65 kU/l, 55% for TATI, and 66% for the combination of CA125 and TATI with cut-off levels of 65 kU/l and 22 micrograms/l. CA125 is the most sensitive marker for epithelial ovarian cancer, but the concomitant measurement of TATI could be of benefit in both differential diagnosis of adnexal masses and monitoring of response of epithelial ovarian cancer to treatment.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

[The maternal-neonatal characteristics of intrauterine growth retardation in a term pregnancy based on a national curve of intrauterine growth].

Using a national curve of fetal growth development, clinical and laboratory characteristics of 100 term neonates small for dates and 130 term adequate for gestational age newborns are studied. A 91% of the small for dates were classified by the ponderal index as having symmetrical growth retardation. At the same time in the 230 mothers we look for clinical features that have been mentioned to produce intrauterine growth retardation. Results showed marked differences (with statistic significance) between both groups of women in relation to: nutritional factors, maternal height, labor activity and presence of oligoamnios. The newborns of both groups didn't show differences, with exception of congenital malformation. The incidence of the classical morbidity of small for dates (asphyxia, hypoglycemia, polycythemia) was no different in both groups. We believe the explanation is that the national curve is more exigent and neonates with higher weight fall under the 10th percentile. We think that in the study group a high percentage of small for dates, are constitutional small and not really growth retarded. We suggest the possibility to use the 5th percentile for better sensibility.

Adolescent↗
PubMed1991

Accessory oculomotor nuclei of man. II. The interstitial nucleus of Cajal: a Nissl and Golgi study.

The interstitial nucleus of Cajal (INC) is an important premotor centre related to the control of eye and head movements. The aim of the present research was to draw a detailed picture of the cytoarchitecture of the human INC, in particular taking into consideration the morphological features of the neurons and their functional implications. Within the neuronal population, two groups of cells were identified: one group (the most substantial) was made up of small and medium-sized neurons showing different soma shapes and both light and moderate basophilia. The second group consisted of a limited number (about 25%) of large cells dispersed throughout the whole INC, showing polygonal soma and intense basophilia. The hypothesis that these large cells represent a different cellular population inside the INC is advanced. On the basis of the dendritic emergence pattern, two types of cells were identified: multipolar and fusiform cells. The multipolar cells (59%) had small to large nerve cell bodies giving off 2-3 dendrites radiating in all directions. Dendrites and axons were often seen spreading outside the INC. The fusiform cells were small or medium sized and two dendrites emerged from the opposite poles of their elongated perikaryon. Their dendrites and axons always lay inside the INC. The fusiform cells were interpreted as neurons carrying out a mainly local integrative function, while the multipolar cells could also probably carry out an important projective role. The structural data reported are in agreement with the functional studies indicating the INC as both an integrative and a projective center.

Adult↗