PubMed Health⌕ Search

Biomedical subjects

S Squatrito

Publications and source records attributed to S Squatrito.

At least 19 recordsLinked to original sources
PubMed1999

Insulin/IGF-I hybrid receptors play a major role in IGF-I signaling in thyroid cancer.

The insulin-like growth factor-I (IGF-I) plays an important role in determining the biological behavior of a variety of malignancies. We measured IGF-I, its receptor and related receptors in thyroid cancer. IGF-I was present both in normal thyroid tissue and in thyroid cancer tissue and it was produced by stromal cells but not by thyrocytes. Values were significantly higher in malignant than in normal tissue. IGF-I receptors (IGF-I-Rs) and the homologous insulin receptors (IRs) were found overexpressed in both thyroid cancer cell lines (n = 4) and specimens (n = 17) as compared to normal values. In addition, high levels of hybrid IGF-I/insulin receptors (IR/IGF-I-Rs) were present in both thyroid cancer specimens and cell lines. IR/IGF-I-R hybrids were the most represented type of receptor in 14/17 specimens and exceeded the IGF-I-R content in all cases. Hybrid content correlated with the IR and IGF-I-R content, suggesting that in thyroid tissue hybrid formation occurs by random assembly of IR and IGF-I-R half receptors. Hybrid receptor autophosphorylation was stimulated by IGF-I with high affinity. In cells with a high IR/IGF-I-Rs content, blocking antibodies specific to these receptors substantially inhibited IGF-I induced cell growth. These data indicate that the IGF-I system is overactivated in thyroid cancer and that IR/IGF-I-R hybrid receptors play an important role in IGF-I mitogenic signaling in these tumors.

Cell Line↗
PubMed1999

Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex.

The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto-occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde fluorescent tracers. Fluoro-Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso-caudal (PMdc, F2) and dorso-rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually-related and eye-position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential 'early' node of the distributed network underlying visually-guided reaching. In this network, reciprocal association connections probably impose, through re-entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.

Animals↗
PubMed1998

Corticocortical connections between frontal periarcuate regions and visual areas of the superior temporal sulcus and the adjoining inferior parietal lobule in the macaque monkey.

In macaque monkeys, corticocortical connections between distinct parietotemporal visual areas (areas MST-FST, DP, and 7a) and frontal periarcuate areas are studied using tritiated aminoacids and WGA-HRP. While labeling within the banks of the principal sulcus, the dorsal part of the arcuate concavity, and the banks of the upper arcuate limb were present in both 7a and MST-FST injected animals; in the latter cases, additional projections were found towards frontal regions including the dorsomedial frontal cortex and the posterior bank of the arcuate ventral limb. Our results point to widespread frontal connections of the MST-FST complex, involving both prefrontal and premotor cortical regions.

Animals↗
PubMed1997

Encoding of smooth pursuit direction and eye position by neurons of area MSTd of macaque monkey.

The spike activity of neurons was recorded from the dorsal bank of the superior temporal sulcus (area MSTd) of alert behaving macaque monkeys performing visual fixation or target tracking tasks, with the aim of studying the tuning features of these neurons with both the direction of slow eye movement and the position of gaze. One hundred thirty-two neurons were tested for several fixation points and tracking directions. Many of them (43%) tuned to the direction of pursuit, regardless of the angle of gaze. Some (18%) showed a tonic discharge modulated by the static position of the eyes without pursuit direction specificity. A substantial number of cells (22%) were characterized by a discharge rate tuned to pursuit direction but influenced also by angle of gaze. Tuning curves for eye movement direction presented an average bandwidth of 130 degrees and turned out to be continuously overlapping, suggesting a sort of vector coding of smooth pursuit direction. Gaze fields of eye position (EP) neurons were mostly ramp-like, with center of ramps shifted away from the straight ahead, implying a form of scalar coding of gaze eccentricity. The different categories of cells were intermingled and close to each other, suggesting possible reciprocal interactions within the same cortical area. These results show that EP and pursuit direction are signaled mainly by separate neuronal elements in area MSTd. Moreover, some cells can integrate both signals. Taking into account the visual responses of MSTd neurons to large, textured, moving fields, it is suggested that this area could be the site of interaction between visuo-oculomotor signals related to visual motion detection, slow eye movement direction, and EP. This signal interaction may be important for integrative functions such as analysis of external or self-induced visual motion, cortical control of pursuit eye movements, and eye/head coordination.

Animals↗
PubMed1997

[Echography at "high resolution" in the diagnosis of cervical lymphadenopathies in follow-up of thyroid carcinoma].

BACKGROUND: In the diagnosis and follow-up of differentiated thyroid cancer (DTC) patients, a major clinical objective is to differentiate whether the cause of enlarged neck lymph nodes is either tumorous or inflammatory. High-frequency (7.5-10 MHz) ultrasound examination proved to be highly informative in this regard. An oval shape of the examined lymph node (longitudinal/anteroposterior diameter ratio, L/A > 1.5) and a central echogenic hilus indicate a benign lymphadenopathy. Roundness (L/A < or = 1.5), absence of the central echogenic hilus and a parenchymatous echogenicity are considered as signs of malignancy. METHODS: A series of 131 lymph nodes in DTC patients were examined at ultrasound and, on the basis of round shape (L/A < or = 1.5) in association with either one or both the other features (absence of central echogenic hilus, homogenous internal echo), 94 lymph nodes were classified a "malignant" and 37 "benign". The ultrasonographic diagnosis was evaluated with either cytologic or histologic diagnosis in all "malignant" nodes and in 7/30 "benign" nodes. In the other 30 "benign" nodes volume shrinkage or lymph node disappearance was observed during follow-up period. RESULTS: According to the results obtained, the ultrasound features utilized provided a good diagnostic accuracy (87%) with only 5 false positive case. CONCLUSIONS: High-frequency sonography, therefore, must be considered a useful and accurate method for evaluating suspected lymphadenopathy in DTC patients.

Follow-Up Studies↗
PubMed1996

Longitudinal study on goiter prevalence and goitrogen factors in northeastern Sicily.

A longitudinal study was carried out in an area of endemic goiter of north-eastern Sicily. Three different surveys (in 1977, 1983 and 1994) evaluated the epidemiological prevalence of goiter in schoolchildren of the endemic area (towns of Bronte, Troina and Maniaci) in comparison to an iodine sufficient control area (Catania). Biochemical studies were also performed on urinary iodine and thiocyanate (SCN) excretion and 131I thyroid uptake. In the town of Troina an experimental program of active iodine prophylaxis was carried out from 1979 to 1987 by iodinating the municipal water supply. The aim of this study was to evaluate the effect of an active iodine prophylaxis program in comparison to the "silent iodoprophylaxis" due to improved economic conditions and widespread introduction of industrially produced food. In the 1977-94 period a significant decrease of goiter prevalence in schoolchildren was observed in all areas where no active iodoprophylaxis had been introduced. An abnormal prevalence of goiter, however, was still present in Bronte (12.1%) and Maniaci (25.9%) schoolchildren in respect to Catania (0.7%). In Troina, goiter prevalence decreased from 52.2 to 6.1% after only five years of active iodine prophylaxis (1983). It increased to 8.4% seven years after the program was discontinued (1994). In all areas studied average urinary iodine excretion increased by 70-100 micrograms/day except in the more rural area at Maniaci. During the same period urinary SCN values decreased by 30-40% and were lower in Troina (non volcanic soil) than in other towns studied. The balance between iodine and SCN intake appears a relevant factor in the etiology of endemic goiter in these areas and the iodine/SCN ratio inversely correlated with goiter prevalence. The persistence of endemic goiter in spite of the important changes in life style and socio-economic conditions if compared to the dramatic amelioration obtained by an active iodine prophylaxis program, confirms the inadequacy of the silent iodine prophylaxis, and further supports the need of an immediate introduction of active iodine prophylaxis in the areas of endemic goiter in Sicily.

Antithyroid Agents↗
PubMed1995

Maternal hypothyroxinaemia during the first half of gestation in an iodine deficient area with endemic cretinism and related disorders.

OBJECTIVE: Iodine deficiency is well known as the cause of several disorders such as endemic goitre and cretinism, along with a wide spectrum of psychoneurological development disorders including endemic mental deficiency and endemic cognitive deficiency, which are generally correlated to damage to the fetus. Such damage is, by inference, deemed a consequence either directly of iodine deficiency or of insufficient availability of thyroxine at the feto-placental unit level. Early pregnancy represents the crucial period for neurogenesis in the embryo. Several experimental studies have emphasized the direct role of maternal T4 in neurological embryogenesis, before the onset of fetal thyroid function and, therefore, its protective role in fetal thyroid failure. The objective of this study was to evaluate whether iodine deficiency may influence thyroid status of pregnant women throughout the first half of pregnancy. DESIGN: Thyroid function tests including total and free T4 and T3, TBG and TSH along with urinary iodine excretion were measured in the serum of pregnant women from an iodine deficient endemic goitre area in north-eastern Sicily, at 8, 13 and 20 weeks of gestation. The times of sampling were chosen to correspond approximately to a period prior to, coincident with and after the onset of fetal thyroid function, respectively. SUBJECTS: The longitudinal study was undertaken in 16 euthyroid pregnant women from the iodine deficient area in which major iodine deficiency disorders such as endemic cretinism and endemic cognitive deficiency in schoolchildren still persist (area A) and in 7 age matched volunteer pregnant women from a marginally iodine sufficient area (area B). MEASUREMENTS: Hormones and TBG were measured using commercial kits. Urinary iodine was measured by an automated method. RESULTS: The divergent changes in serum T4 and TBG with pregnancy progression induced a progressive TBG desaturation by T4 during the whole study period (from 22 to 17% in area A, ANOVA two-way F = 18.9, P < 0.0001; from 33 to 20% in area B, F = 20.7, P < 0.0005) in both areas. At 20 weeks, average FT4 levels were lower in area A than in area B (11.5 +/- 2.5 vs 14.3 +/- 2.4 pmol/l, t = 2.7 P < 0.01) and were below the normal range in 2/16 and borderline-low in 6/16 pregnant women. FT4 serum levels were inversely related to TSH concentrations (r = -0.54, P < 0.0001) which progressively increased, in area A, during the whole study period (F = 6.0, P < 0.01) and were abnormally high in the two women with low FT4, but not in area B. Also in area A (F = 3.4, P < 0.05) a significant T3/T4 molar ratio increase was observed. CONCLUSIONS: Iodine deficiency induces in early pregnancy a series of events (reduced synthesis of maternal T4, TBG desaturation by T4, critical decrease of FT4 levels with consequent TSH increase) responsible for overt or marginal biochemical hypothyroidism in about 50% of pregnant women. It is hypothesized that the imbalance of maternal thyroid hormone homeostasis during pregnancy as a consequence of endemic iodine deficiency may be responsible for the impaired psychoneurological development observed in children from that area so appropriate iodine and/or thyroxine prophylaxis to women in that region may prevent the neurobehavioural, cognitive and motor compromise of the population.

Adolescent↗
PubMed1994

Incidence of type I diabetes in the district of Catania, Sicily.

The incidence of type I (insulin-dependent) diabetes was determined in the district of Catania (eastern Sicily) in children under 15 years of age over a 3-year period (1 January 1989 to 31 December 1991). Two independent sources of information were used. The primary source was contact with all medical services in the province, and the secondary source was the personal identification cards issued to all diabetic patients by the National Health System necessary for obtaining free medical care. The information obtained was 99.6% complete. The overall incidence was 10.2/10(5) per year. This study provides the first standardized data on the incidence of type I diabetes in Sicily and is consistent with the possibility of regional deviations from the proposed north to south gradient.

Adolescent↗
PubMed1992

Comparison of combined therapies in treatment of secondary failure to glyburide.

OBJECTIVE: To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment. RESULTS: Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients. CONCLUSIONS: The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Blood Glucose↗
PubMed1992

Projections from cortical visual areas of the superior temporal sulcus to the superior colliculus, in macaque monkeys.

1. The distribution of tectal projections of two visual areas of the superior temporal sulcus (MT and MST areas) has been studied, in five Macaca fascicularis, by means of the autoradiographic method tracing the anterograde transport of tritiated aminoacids intracortically injected. 2. In all cases the ipsilateral superior colliculi (SC) were found labelled, whereas the contralateral ones were devoid of label. 3. The three brains injected in the MT area resulted in SC labels that involved the superficial gray layer (SGS), the stratum opticum (SO) and the intermediate gray layer (SGI), sparing the layers below SGI. 4. The collicular labels found after injections within the MST area exhibited their distribution over the deep SC subdivision, whereas they spared all the superficial layers but the deep part of the SO. 5. In two animals with large uptake zones, one in MT and the other in MST, the labelling within the SGI showed a cluster-like pattern. 6. The distinct found bulk of projections of MT and MST respectively to the superficial and deep subdivisions of the SC, along with a number of peculiar connections of the MST area as mentioned in the text, contribute to depict an overall neural network in which MST appears to be more strongly involved than MT in linking sensory visual with oculomotor attentive functions.

Afferent Pathways↗
PubMed1991

Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide.

In this study we compared, in 12 NIDDM patients with secondary failure to glyburide, the effect of adding either a single, low-dose bed time NPH insulin injection (0.2 U/Kg) or an oral metformin administration (500 mg x 3) to the previously ineffective sulfonylurea treatment. The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1. The effect of both combined therapies was already evident and maximal after 2 weeks of treatment. The addition of bed-time NPH insulin caused a greater decrease of fasting plasma glucose, although the difference with the addition of metformin was not significant. In contrast, the average post-prandial plasma glucose decrease was significantly greater after metformin addition. The addition of bed-time NPH insulin caused a significant increase in average body weight, while after metformin addition, average body weight was unchanged; no change in the average cholesterol and triglyceride level was observed after either combined therapies.

Adult↗
PubMed1990

Influences of uniform and textured backgrounds on the impulse activity of neurons in area V1 of the alert macaque.

The influences of the visual background on the spontaneous and evoked activity of neurons in the striate cortex (V1) of the awake and behaving macaque were investigated using uniform (dark and bright) and textured (dynamic random-dot) large fields (10 degrees) centered on the receptive field of the cell under study. Rhesus monkeys were trained to fixate a small target while visual patterns were presented on monitor displays and the impulse activity of single cortical neurons recorded extracellularly with metal microelectrodes. The discharge rates of the ongoing, spontaneous activity of the vast majority of V1 neurons, as well as their responses to optimally adjusted bar stimuli, were not significantly influenced by the luminance of a uniform background. On the other hand, the activity of more than 50% of V1 neurons was clearly affected by a textured background. Comparison of the effects of a uniformly dark background and a background of dynamic random dots showed that the neuron's spontaneous discharge rate was typically higher in the presence of the textured background, while the evoked response was often reduced in amplitude or even suppressed. The opposite effects were observed in only a few neurons. These findings indicate that neurons in area V1 are highly sensitive to a textured background of dynamic random dots which exert on them an activating effect, chiefly by stimulation of the neuron's receptive field, with consequent increase in the ongoing discharge and a reduction of the dynamic range of impulse activity, leading to a reduction in the amplitude of the response evoked by a contrast stimulus.

Action Potentials↗
PubMed1990

Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients.

This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1989

Projections from visual cortical areas of the superior temporal sulcus to the lateral terminal nucleus of the accessory optic system in macaque monkeys.

Tritiated amino acids were injected into the striate area and in single visual areas of the superior temporal sulcus (STS) of 7 cynomolgus monkeys, in order to trace visual cortical projections to the nuclei of the accessory optic system (AOS). Injections in STS separately involved the areas MT and MST, and resulted in labels within the lateral terminal nucleus of the AOS. In no case were labels found within the AOS nuclei in the brains injected in the striate area, or within the contralateral AOS. It seems likely that the areas MT and MST contribute signals--selectively related to visual motion processing--to the AOS, which is probably involved in the neuronal pathway subserving the optokinetic reflex.

Animals↗
PubMed1989

Low-dose bedtime NPH insulin in treatment of secondary failure to glyburide.

Secondary failure to oral hypoglycemic agents (OHAs) is a possible outcome for non-insulin-dependent diabetes mellitus (NIDDM) patients and poses a serious therapeutic problem. In this study, we evaluated the effect of adding a single bedtime low-dose NPH insulin injection to the previous ineffective sulfonylurea therapy in 23 NIDDM patients with true secondary failure to OHAs. This treatment schedule was conducted for 3 mo by 18 patients (78%) who completed the study. In these patients, the addition of NPH insulin (0.2 +/- 0.01 IU/kg body wt) greatly decreased fasting and postprandial plasma glucose (P less than .001) and glycosylated hemoglobin (P less than .005). No weight gain was observed in any of the patients studied. Five patients dropped out: 2 patients (9%) due to insufficient compliance, 2 patients (9%) due to the multiple insulin injections required to achieve good metabolic control, and 1 patient (4%) due to recurrent hypoglycemic episodes. No correlation was observed between glucagon-stimulated C-peptide values and amelioration of metabolic control. In conclusion, most NIDDM patients with secondary failure to OHAs may be successfully treated with the addition of a single low-dose bedtime NPH insulin injection, and residual beta-cell function evaluation is not able to predict the effectiveness of the combined treatment.

C-Peptide↗
PubMed1989

Evaluation of albumin excretion rate in overnight versus 24-h urine.

This study was performed to assess whether the albumin excretion rate (AER) measured in overnight urine (N-AER) and 24-h urine (24-h AER) gives comparable results. For this reason we evaluated N-AER and 24-h AER on the same day from 35 control subjects, 57 patients with insulin-dependent diabetes mellitus (IDDM), and 63 patients with non-insulin-dependent diabetes mellitus (NIDDM). AER values obtained from the two urine collection procedures were significantly different (P less than .01), with 24-h AER approximately 30% higher than N-AER. Moreover, when the same cutoff value (20 micrograms/min) was used to define the normal range, 21% of IDDM patients and 6.3% of NIDDM patients had on the same day normal N-AER and abnormal (greater than 20 micrograms/min) 24-h AER. Although N-AER values were significantly correlated to 24-h AER values (r = 0.67, P less than .001), it was not possible to assess an N-AER value able to predict a 24-h AER value greater than 20 micrograms/min. In conclusion, N-AER and 24-h AER cannot be used as an equivalent method to establish AER.

Albuminuria↗
PubMed1988

Insulin degradation into monocytes from normal subjects: a high performance liquid chromatographic analysis.

In this work the fate of A14-125 I-insulin inside human cells has been investigated by the complementary use of gel permeation and reversed-phase high performance liquid chromatography to obtain a better resolution of the cell processed radioactive material resulting from the internalization of labeled insulin. Mononuclear leukocytes from 12 normals were incubated with pure A14-125 I insulin at 37 C and internalized radioactivity was characterized after 2, 15 and 60 min. Nearly 14% of intracellular radioactivity was associated to materials with a molecular weight of approximately 300,000. The remaining 86% had a molecular weight lower than 20,000. High molecular weight material showed an elution profile very similar to that obtained from purified human placental insulin receptor and was partially precipitable with antireceptor antibody. The reversed phase high performance liquid chromatography analysis of the low molecular weight material showed two main peaks corresponding to 125 I and A14-125 I-insulin and three intermediate peaks, a, b, c, accounting for about 8% of the recovered radioactivity. By increasing the incubation time of A14-125 I-insulin with monocytes a decrease of insulin peak (2 min: 38 +/- 18%; 15 min: 25 +/- 11%; 60 min: 6 +/- 4%) and a corresponding increase of iodide peak was observed. Immunoprecipitability with anti-insulin antibody was 0% for iodide and a peaks, 60% for peak b, 78% for peak c and 90% for A14-insulin peak. Our results show that intracellular insulin degradation procedes rapidly and in a time-dependent manner and that this process produces insulin derivatives which partially retain the immunological properties of intact A14-125 I insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗