Diabetic neuropathy and the pharmacology of gangliosides.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R Bianchi
Publications and source records attributed to R Bianchi.
Effectiveness of the health campaign for the early diagnosis of cutaneous melanoma in Trentino, Italy.
BACKGROUND: To reduce the mortality rate from cutaneous melanoma in Trentino, a health campaign for early diagnosis aimed at the general public was organized. OBJECTIVE: The mortality rate from cutaneous melanoma in Trentino before and after our health campaign was analyzed and compared with the mortality rates in three neighboring regions where no campaigns were carried out. METHODS: The mortality for cutaneous melanoma was analyzed using data from the death certificates provided by ISTAT for the pre- and postcampaign periods. The two summary methods: cumulative rate and the standard mortality ratio were used. RESULTS: The cumulative mortality rates in the neighboring regions show a tendency to increase over the three periods whereas the increase in Trentino is less evident. The standard mortality ratios confirmed this result. CONCLUSION: We feel that this type of campaign is to be recommended in the reduction of mortality from cutaneous melanoma.
Death Certificates↗
Disposal and distribution of rT3 in humans: a new double-tracer kinetic study.
A satisfactory definition of reverse 3,3',5'-triiodothyronine (rT3) kinetics in humans cannot be obtained if the plasma disappearance curve of the injected labeled hormone is the only experimental data available; most of the kinetic parameters can only be bounded within ranges showing unacceptable variabilities. To gain additional experimental data a double-tracer approach is proposed. After simultaneous injection of [125I]rT3 and 131I the following three experimental curves were determined in plasma: 1) the disappearance of [125I]rT3, 2) the disappearance of 131I, and 3) the appearance of 125I generated in vivo from labeled rT3 degradation. Combined analysis of these three curves, based on a complex six-compartment model, was developed and applied to data obtained in a group of normal subjects. Through this new analysis, fractional disposal rates and fractional exchange rates between the plasma compartment and the periphery are uniquely determined. The main physiologically interesting information on the degradation of the hormone that emerges from these studies are 1) all degradative pathways of rT3 generate iodide, being in all cases the [125I]rT3 dose completely recovered as 125I in plasma; and 2) most rT3 is degraded (65-90%) in peripheral tissues rapidly exchanging with the plasma pool. The extended experimental base is not yet sufficient to compute unique values for production rate (PR) and body mass (Qt); the validity of estimates of PR and Qt is based on the assumption that injected [125I]rT3 is able to trace all rT3 peripherally produced (from thyroxine). The new approach yields ranges for PR and Qt (1.12-2.15 micrograms/h and 2.88-8.24 micrograms) much narrower than those computable from the [125I]rT3 disappearance curve only (1.12-5.07 micrograms/h for PR and 2.88-23.7 micrograms for Qt).
Adult↗
ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake.
125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were derived from the disappearance curves of the 125I-ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet.
Adult↗
Serum soluble interleukin-2 receptor assay in epithelial ovarian cancer.
Preoperative serum soluble interleukin-2 receptor (sIL-2R) and CA 125 levels were measured in 183 patients with ovarian masses undergoing laparotomy. Serum sIL-2R levels were higher in the 54 patients with epithelial ovarian cancer than in the 129 patients with benign ovarian diseases (p < 0.0001). Elevated serum levels of sIL-2R (> or = 71 U/ml) and CA 125 (> or = 83 U/ml) were found in 79.6 and 77.8% of patients with epithelial ovarian cancer, respectively. Serum sIL-2R and CA 125 positivity rates correlated with the FIGO stage (p = 0.0033 and p = 0.0001, respectively). Raised serum levels of sIL-2R and CA 125 were detected in 11.6 and 7.0% of patients with benign ovarian diseases, respectively. The combination sIL-2R or CA 125 had a sensitivity of 88.9%, and the association sIL-2R and CA 125 had a specificity of 98.4% for epithelial ovarian cancer. As for the 16 patients with this malignancy who were serially monitored during and after chemotherapy, changes in sIL-2R and CA 125 levels correlated with the clinical course of disease in 62.3 and 94.3% of 53 instances, respectively. In conclusion, the serum sIL-2R assay could represent a useful adjunctive tool for the differential diagnosis of ovarian masses, while it seems to be of limited benefit for monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer.
Adolescent↗
Simultaneous recording of blood volume shifts in different vascular beds in man by a versatile scintigraphic method.
A device was developed to record the blood volume changes occurring in the lung and calf during postural changes, physical exercise, and the Valsalva maneuver in man. The changes in regional counting rates from the right middle lung and the calf mirrored the well-known changes in venous return that are expected to occur in response to the above-mentioned external stimuli. Thus a sustained decrease in lung blood volume was noted on assumption of the erect posture as well as during the forced expiration of the Valsalva maneuver. In addition a rapid increase and a sharp decrease in lung blood volume took place at the very onset and at the very end of walking, respectively. The calf blood volume declined immediately at the onset of walking, increased slightly in the ensuing two minutes, and returned to baseline quickly at the termination of walking. The authors' method enables real-time equilibrium blood pool scintigraphy to be recorded continuously and simultaneously from different districts over sustained periods of time irrespective of the posture and the physical activity performed by the patient. Their method might improve knowledge of the systemic circulatory responses to selective physiologic and therapeutic interventions in health and disease.
Blood Volume↗
Direct inhibitory effect of somatostatin on the growth of the human prostatic cancer cell line LNCaP: possible mechanism of action.
The effects of somatostatin-14 (S) on the proliferation of the human prostatic cancer cell line (LNCaP, lymph node carcinoma of the prostate) and on the amount of proteins secreted by these cells have been studied. LNCaP cells were treated for 3 days with different doses of S. The hormone significantly inhibits cell proliferation at doses comprised between 0.4 and 2 nmol, as indicated by a significant decrease in the incorporation of 3H-thymidine as well as in the uptake of [alpha-32P]dATP. The direct antiproliferative effect of S is reversible, since cell proliferation returns to normal 4 days after withdrawal of the hormone from the medium. This action of S is not due to cytotoxic side-effects, since no changes in the incorporation of 35S-methionine are observed. Total RNA and protein synthesis do not appear to be modified by the hormone in vitro. The hormone probably exerts its antiproliferative effect on LNCaP cells by stimulating phosphotyrosyl protein phosphatases, since the inhibition of growth induced by S (1 nmol) is reversed by sodium vanadate (2 and 4 mumol), a potent inhibitor of the process of tyrosine dephosphorilation. In addition, S (1 nmol/L) induces a significant decrease in the amounts of proteins secreted by LNCaP cells. Also the antisecretory action of S seems to be mediated by the activation of phosphotyrosyl protein phosphatases, since sodium vanadate is able to reverse the action of S on this parameter. In conclusion, the present data suggest for the first time that S exerts a direct inhibitory effect on LNCaP cell proliferation and protein secretion, two effects probably mediated by the activation of phosphotyrosyl protein phosphatases.
Cell Division↗
Effects of benfluorex on insulin resistance and lipid metabolism in obese type II diabetic patients.
OBJECTIVE: To evaluate the change in lipids and insulin sensitivity in 10 obese type II diabetic patients after treatment with benfluorex or placebo for 2 wk. RESEARCH DESIGN AND METHODS: The study had a double-blind, cross-over design. Insulin sensitivity was measured with the euglycemic hyperinsulinemic glucose clamp technique at two different insulin infusion rates: 0.05 (clamp 1) and 0.10 U.kg-1.h-1 (clamp 2). RESULTS: Subanalysis of the glucose infusion rate under steady-state conditions in the last 30 min of clamp 2 yielded a glucose infusion rate of 5.36 and 3.87 mmol.kg-1.min-1 after benfluorex and placebo, respectively (P = 0.018). CONCLUSIONS: Benfluorex increases insulin sensitivity in obese type II diabetic patients.
Apolipoprotein A-I↗
Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.
Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.
Adolescent↗
The ultrastructural organization of the nucleus of the posterior commissure of rat.
An electron microscope study was carried out to clarify the ultrastructure of the nucleus of the posterior commissure (NPC) of rat which is thought to be related to the eye movements and oculomotor reflexes. The neurons were small or medium-sized, loosely arranged in an extensive neuropil. The nerve cell bodies showed a high nucleocytoplasmatic ratio, scanty endoplasmic reticulum and very few axo-somatic contacts. The synaptic boutons were very numerous in the neuropil, thus indicating the latter as the main target for inputs to the NPC. The majority of the synapses showed the typical morphological features of the excitatory synapses and so it was hypothesized that a mainly excitatory activity takes place in the NPC. Since the NPC, together with the nucleus of Darkschewitsch (ND) and the interstitial nucleus of Cajal (INC) belongs to the accessory oculomotor nuclei, a comparison of their ultrastructure was carried out.
Animals↗
Accessory oculomotor nuclei of man. III. The nuclear complex of the posterior commissure: a Nissl and Golgi study.
A morphoquantitative study was carried out to clarify the cytoarchitecture of the human nuclear complex of the posterior commissure (NPC), a collection of cell groups which is thought to be involved in the pupillary light reflex and eye movements. On the basis of the topographical features, 5 different parts (rostral, principal, magnocellular, subcommissural and infracommissural) were identified in NPC. In these 5 parts, the neuronal population consisted of small and medium-sized neurons with a structural pattern similar to that of the central reticular formation. The only exception was the magnocellular part in which the neurons, mainly medium-sized and large, did not show the reticular-like features. In the Golgi material, two types of NPC neurons were identified: multipolar and fusiform cells. In the multipolar cells, 2-3 dendrites emerged from the soma and gave off a wide dendritic arborization. Many of the dendrites and axons of the multipolar cells were seen spreading outside NPC. The fusiform cells had 2 dendrites emerging from the opposite poles of their elongated perikaryon. Dendrites and axons of the fusiform cells always lay inside NPC. These observations suggest that the multipolar cells are mainly projective neurons and that the fusiform cells are neurons which mainly perform a local integrative function. Since the present study concludes our investigation of the human accessory oculomotor nuclei, a comparison of their structure was carried out. All the nuclei showed a common reticular-like structure, although each nucleus had its own structural particularities.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
S-100 protein binds to annexin II and p11, the heavy and light chains of calpactin I.
S-100 protein, a dimeric, Ca(2+)-binding protein of the EF-hand type, interacts with annexin II (p36, the heavy chain of the cytoskeletal protein complex, calpactin I), with p11 (the light and regulatory chain of calpactin I) and with the hetero-tetramer annexin II2-p11(2) (calpactin I) in a Ca(2+)-regulated way, but not with annexins I, V and VI. The interaction of S-100 protein with the above proteins was investigated by fluorescence spectroscopy using acrylodan-S-100 protein and acrylodan-annexin II and by cross-linking experiments using the bifunctional cross-linker disuccinimidyl suberate (DSS). S-100 protein binds with the highest affinity to annexin II (Kd approx. 0.4 microM) and with the lowest affinity to calpactin I (Kd approx. 10 microM), with a constant stoichiometry of about 2 mol of protein/S-100 dimer. Thus, S-100 protein could substitute for p11 in regulating the activities of annexin II in cells which do not express p11 and/or act synergistically with p11 in cells expressing both p11 and S-100. The binding of S-100 protein to p11 could reflect the natural tendency of S-100 subunits and p11 to dimerize. Chimeric p11-S-100 alpha and p11-S-100-beta proteins could therefore form in a Ca(2+)-regulated way. The interaction of S-100 protein with calpactin I appears of doubtful physiological importance, because of the low binding affinity, of the small extent of fluorescence changes induced by calpactin I in acrylodan-S-100 protein and of lack of DSS-induced complex formation between the two protein species.
2-Naphthylamine↗
Novel isoforms of CaBP 33/37 (annexin V) from mammalian brain: structural and phosphorylation differences that suggest distinct biological roles.
Two calcium-dependent phospholipid- and membrane-binding proteins have been purified from bovine brain. These are termed CaBP33 and CaBP37. Complete sequence analysis has revealed that these two proteins are isoforms of annexin V. Despite an apparent difference of 4 kDa between the two proteins on SDS-PAGE, only two amino-acid substitutions were found. These are, in CaBP33, Ser-36 and Lys-125 and in CaBP37, Thr-36 and Glu-125. This corresponds to a mass difference of 15 Da. This was confirmed by electrospray mass spectrometric analysis. Both isoforms can be phosphorylated substoichiometrically in vitro by protein kinase C at residue Thr-22.
Amino Acid Sequence↗
A new method for evaluating lung uptake of thallium-201 during stress myocardial scintigraphy.
A novel, multipurpose device has been designed that allows thallium activity to be continuously studied from a given lung area at rest and at peak exercise. The information gained from this technique proves to be relevant and reliable because lung thallium activity is displayed in real time and the interpretation of thallium distribution is not based on qualitative or quantitative comparison with that in the myocardium or mediastinum. The time-activity curves obtained in our study group are reported and the relation of peak activity to plateau activity (peak/plateau ratio) is proposed as an index that is easy to obtain for identifying patients with normal and impaired left ventricular function.
Adult↗
Immunogenic tumor variants induced by drug treatment of the L5178Y lymphoma: search for serologically defined antigens at the clonal level.
Highly immunogenic tumor variants are generated by in vitro or in vivo treatment of the murine L5178Y lymphoma line with triazene derivatives. Most of these variants express new transplantation- and antibody-defined antigens that previous studies have shown to be closely related. One such 80-kDa protein on the surface of clone-D cells was found to be related to xenotropic MuLV gp70 molecules. To investigate the possible relevance of clone-D data to general properties of immunogenic variants in this tumor model system, polyclonal syngeneic antisera raised to a panel of immunogenic clones (including clone D) of the drug-treated L5178Y lymphoma line were employed in the immunoprecipitation of cell-surface and intrinsically labeled variant cells. In all clones, 1- and 2-dimensional electrophoretic analysis of the immunoprecipitates detected an antigen of approximately 80 kDa, and 35S-labeled 80-kDa molecules could be cross-precipitated from all clones by the panel of clone-specific antisera. In addition, 45- and 30-kDa components were also found in metabolically labeled variant cells. While the surface 80-kDa component was reactive with anti-xenotropic gp70 antibodies, the 30-kDa molecule was removed by anti-gag p30 antibody in sequential immunoprecipitation experiments. These data suggest that expression of aberrant, retrovirus-related proteins is a common finding in immunogenic cells of the drug-treated L5178Y lymphoma line.
Animals↗
Galanin reduces PDBu-induced protein phosphorylation in rat ventral hippocampus.
The effect of galanin (GAL) on basal and phorbol-12,13-dibutyrate (PDBu) induced protein phosphorylation in rat ventral hippocampal miniprisms was investigated. GAL (0.5, 1 and 2 microM) inhibited PDBu stimulation in a concentration-dependent manner without altering basal protein phosphorylation. This inhibitory effect was prevented by the GAL antagonist galantide. GAL did not affect either the activity of protein kinase C (PKC) from rat brain or basal phosphorylation in ventral hippocampal hippogenates, suggesting that it did not directly modulate PKC activity. Depolarization of miniprisms from ventral hippocampi by 18 mM K+ prevented the effect of GAL on PDBu-induced phosphorylation. The results indicate that GAL indirectly regulates neuronal protein phosphorylation by a GAL receptor-mediated action.
Animals↗
Modulation of ATPase activity by cholesterol and synthetic ether lipids in leukemic cells.
Synthetic ether lipids (EL) exert their antiproliferative action on leukemic cells through localization in the plasma membrane with subsequent biochemical effects which are still being elucidated. In the present study, the modulation of membrane-linked ATPase activity was investigated in relation to changes in membrane fluidity of HL60 and K562 human leukemic cells. Incubation of HL60 and K562 cells with EL under non-cytotoxic conditions caused significant membrane fluidization which was related to the membrane cholesterol (CHOL) levels. HL60 cells, which are sensitive to the cytotoxic action of EL, had a lower basal CHOL content. When HL60 cells were loaded with CHOL, Na+, K(+)-ATPase activity was reduced significantly compared to that of untreated cells. In contrast, CHOL-deprived K562 cells had twice the Na+,K(+)-ATPase activity of unmodified K562 cells. Na+K(+)- and Mg(2+)-ATPase activities were stimulated significantly in both cell lines by EL at concentrations lower than 20 microM. This stimulation was greater in cells richer in CHOL, such as K562 cells and CHOL-enriched HL60 cells. In contrast, Na+,K(+)-ATPase in both cell lines was inhibited by EL above 20 microM regardless of the CHOL content. Mg(2+)-ATPase activity was not related to cell CHOL content and was not inhibited by EL above 20 microM.
Bone Marrow↗
Membrane-bound annexin V isoforms (CaBP33 and CaBP37) and annexin VI in bovine tissues behave like integral membrane proteins.
The distribution of annexin V isoforms (CaBP33 and CaBP37) and of annexin VI in bovine lung, heart, and brain subfractions was investigated with special reference to the fractions of these proteins which are membrane-bound. In addition to EGTA-extractable pools of the above proteins, membranes from lung, heart, and brain contain EGTA-resistant annexins V and VI which can be solubilized with detergents (Triton X-100 or Triton X-114). A strong base like Na2CO3, which is usually effective in extracting membrane proteins, only partially solubilizes the membrane-bound, EGTA-resistant annexins analyzed here. Also, only 50-60% of the Triton X-114-soluble annexins partition in the aqueous phase, the remaining fractions being recovered in the detergent-rich phase. Altogether, these findings suggest that, by an as yet unknown mechanism, following Ca(2+)-dependent association of annexin V isoforms and annexin VI with membranes, substantial fractions of these proteins remain bound to membranes in a Ca(2+)-independent way and behave like integral membrane proteins. These results further support the possibility that the above annexins might play a role in membrane trafficking and/or in the regulation of the structural organization of membranes.
Animals↗