Characterization of yeast type-II geranylgeranyltransferase.
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Alkyl and Aryl Transferases↗
Biomedical subjects
G Rossi
Publications and source records attributed to G Rossi.
Dosimetry of 169 Yb seed model X1267.
Unlike previous brachytherapy sources a number of published studies have been addressed to the dosimetry of 169 Yb seeds, manufactured in several prototypes, before widespread clinical use has been made. Discrepancies seen in the dosimetry obtained for ytterbium seed prototypes appear to be related to inconsistency and non-reproducibility in the vendor's calibration procedure to determine contained activity. Av. The comparison of 169 Yb seed dosimetries demonstrates a need for more accurate implementation of calibration procedures to determine the air kerma rate for the definitive 169 Yb seed design. This paper reports an experimental procedure to determine the reference air kerma rate, Kr (mu Gy h-1), defined as the kerma rate at 1 m along the source transverse axis in free space for the new 169 Yb seed, model X1267. A mean value of the ratio Kr/Av = 1.53 mu Gy h-1 mCi-1 was obtained from determining the Kr value of eleven seeds. Since this ratio is only 3% less than the air kerma rate constant for the 169 Yb point source, (gamma delta)k = 1.58 mu Gy h-1 m2 mCi-1, this means that the Av is closer to an apparent activity than a contained activity, Ac. A Monte Carlo simulation to determine the ratio between reference air kerma rate and the contained activity gave Kr/Ac = 1.33 mu Gy h-1 mCi-1. For the dose rate constant in water we obtained DKr (1, pi/2) = 1.20 +/- 0.05 cGy h-1 (mu Gy h-1)-1, using calibrated thermoluminescent dosimeters (TLDs) and DKr (1, pi/2) = 1.21 +/- 0.03 cGy h-1 (mu Gy h-1)-1 by Monte Carlo simulation. TLDs were used both to determine the radial dose distribution along the seed transverse axis and to calibrate GAFChromic films to obtain the two-dimensional dose distribution around the seed.
Biophysical Phenomena↗
BET3 encodes a novel hydrophilic protein that acts in conjunction with yeast SNAREs.
Here we report the identification of BET3, a new member of a group of interacting genes whose products have been implicated in the targeting and fusion of endoplasmic reticulum (ER) to Golgi transport vesicles with their acceptor compartment. A temperature-sensitive mutant in bet3-1 was isolated in a synthetic lethal screen designed to identify new genes whose products may interact with BET1, a type II integral membrane protein that is required for ER to Golgi transport. At 37 degrees C, bet3-1 fails to transport invertase, alpha-factor, and carboxypeptidase Y from the ER to the Golgi complex. As a consequence, this mutant accumulates dilated ER and small vesicles. The SNARE complex, a docking/fusion complex, fails to form in this mutant. Furthermore, BET3 encodes an essential 22-kDa hydrophilic protein that is conserved in evolution, which is not a component of this complex. These findings support the hypothesis that Bet3p may act before the assembly of the SNARE complex.
Amino Acid Sequence↗
Interactive effect of cigarettes and coffee on daytime systolic blood pressure in patients with mild essential hypertension. HARVEST Study Group (Italy). Hypertension Ambulatory Recording VEnetia STudy.
OBJECTIVE: To test the hypothesis that moderate smoking (fewer than 20 cigarettes/day) and coffee consumption have an interactive effect on ambulatory blood pressure. DESIGN: A case-control study. SETTING: Patients in the multicentre Hypertension Ambulatory Venetia Study, northeastern Italy. SUBJECTS: Six hundred and forty-three men and 244 women with borderline-to-mild status (non-smokers versus smokers) and their habitual consumption of coffee (0, 1-3, or 4+ cups/day). MAIN OUTCOME MEASURES: Office blood pressure, ambulatory blood pressure, urinary adrenaline and noradrenaline levels according to smoking status, coffee consumption and their interaction. RESULTS: In the men, daytime systolic blood pressure (SBP) was significantly higher in the smokers than in the non-smokers and in the coffee drinkers than in the others. Moreover, two-way analysis of covariance revealed a significant interaction between smoking status and coffee consumption: the daytime SBP in smokers who drank 4+ cups/day of coffee was 6.0 mmHg higher than that of non-smokers who abstained from coffee. Conversely, office blood pressure was lower in the smokers than in the non-smokers and was similar in the coffee drinkers and the others. Coffee consumption had a significant effect on urinary adrenaline. Similar results were obtained in the women. CONCLUSIONS: In contrast with what is shown by office blood pressure measurement, moderate smokers and coffee drinkers with mild hypertension have significantly higher daytime SBP levels than non-smokers and those who do not drink coffee. Cigarettes and coffee have an interactive effect on daytime SBP in young patients, with mild essential hypertension.
Adolescent↗
Immunoreactive endogenous ouabain in primary aldosteronism and essential hypertension: relationship with plasma renin, aldosterone and blood pressure levels.
OBJECTIVE: To investigate the role of ouabain in human hypertension and to establish whether immunoreactive endogenous ouabain is secreted by the adrenal gland under the influence of dopaminergic regulation. METHODS: We measured plasma levels of endogenous ouabain by immunoassay, together with other variables, including plasma renin activity and aldosterone levels, in 91 clinically selected hypertensives and 19 healthy volunteers. We also measured endogenous ouabain in adrenal venous blood and the effect of DA2 dopaminergic receptor blockade and stimulation. After a thorough clinical evaluation, 64 patients were diagnosed with essential hypertension and 24 with primary aldosteronism. RESULTS: Plasma levels of endogenous ouabain were higher in essential hypertensives than in controls. Multiple regression analysis showed a significant relationship of mean blood pressure with plasma endogenous ouabain, age and body mass index, but not with other measured parameters. The plasma levels of endogenous ouabain were more than two standard deviations above the mean value for normotensives in 45% of patients with essential hypertension in whom plasma renin activity was normal. Higher plasma levels of endogenous ouabain were found in patients with aldosterone excess, specifically affecting 56% of 17 patients with surgically confirmed adrenal cortical adenoma and one (14%) of seven patients with idiopathic causes. Removal of adenomas lowered blood pressure in half of the patients in whom plasma levels of endogenous ouabain normalized after surgery. Plasma endogenous ouabain levels were similar in venous blood from the adrenal and inferior vena cava, and plasma levels were not influenced by DA2 dopaminergic blockade and stimulation. CONCLUSION: Approximately half of Caucasian patients with essential hypertension and with hyperaldosteronism exhibit elevated circulating levels of endogenous ouabain. The latter do not appear to be secondary to hypertension, are unrelated to plasma renin activity, and may not involve adrenal type-2 dopaminergic receptors.
Aldosterone↗
Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections.
The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%): no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1 + myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.
Adolescent↗
Endothelin-1 and its receptors A and B in human aldosterone-producing adenomas.
Endothelin-1 stimulates aldosterone secretion by interacting with specific receptors. Accordingly, we wished to investigate endothelin-1, endothelin-A (ETA) receptor, and endothelin-B (ETB) receptor gene expression, localization, and properties in aldosterone-producing adenomas and in the normal human adrenal cortex. We carried out 125I-endothelin-1 displacement studies with cold endothelin-1, endothelin-3, the specific ETA antagonist BQ-123, and the specific ETB weak agonist sarafotoxin 6 C and coanalyzed data with the nonlinear iterative curve-fitting program LIGAND. We also studied gene expression with reverse transcription-polymerase chain reaction with specific primers for endothelin-1, ETA, and ETB complementary DNA. Normal adrenal cortices from consenting kidney cancer patients (n = 2) and aldosterone-producing adenomas (n = 4) were studied; for the latter, surrounding normal cortex and kidney biopsy tissue served as controls. To further localize the receptor subtypes, tissue sections were studied by autoradiography in the presence and absence of 500 nmol/L BQ-123, 100 nmol/L sarafotoxin 6 C, and 1 mumol/L cold endothelin-1. In all tissues examined, endothelin-1, ETA, and ETB messenger RNAs were easily detected. However, in aldosterone-producing adenomas, both receptors' genes were expressed at a higher level than in the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Hypertensive cerebrovascular disease and the renin-angiotensin system.
BACKGROUND: Arterial hypertension is the leading cause of cardiovascular disease and is associated with an increased risk of stroke and heart attack. These complications have been largely attributed to the remodeling of the arterial wall, including accelerated atherosclerosis occurring in hypertensive patients. Although the risk of haemorrhagic stroke seems to be directly related to the level of blood pressure elevation, no such tight relationship has been found between blood pressure levels and atherosclerosis. This observation has led to the concept that a number of genetic, humoral, and cellular factors may be involved in atherogenesis in hypertensive patients. SUMMARY OF REVIEW: The experimental and clinical evidence concerning the role of the renin-angiotensin system in cardiovascular remodeling and atherogenesis of the cerebrovascular bed as well as the data supporting an association between angiotensin II and thrombotic stroke are examined. CONCLUSIONS: The contribution of the renin-angiotensin system to the pathogenesis of accelerated carotid artery atherosclerosis and particularly of cerebrovascular disease remains to be definitively proven. However, the bulk of experimental and clinical data are consistent with the hypothesis that the renin-angiotensin system may play a detrimental role.
Angiotensin II↗
Thyroid C-cells carcinoma in a sheep: histopathological and immunocytochemical study.
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Amyloid↗
Retinoic acid induces intercellular adhesion molecule-1 hyperexpression in human thyroid carcinoma cell lines.
The expression of intercellular adhesion molecule-1 (ICAM-1) in tumoral tissues may promote their interaction with the immune system and cytotoxic effect on tumoral cells. This observation led to the investigation of ICAM-1 expression and modulation in different tumoral cell systems in vitro. Recently, retinoic acid-responsive elements have been found in the 5'-regulatory region of the human ICAM-1 gene. In the present study, we investigated, by flow cytometry, the effect of retinoic acid on the surface expression of ICAM-1 in human thyroid carcinoma cell lines. Two papillary (NPA and TPC-1), one follicular (WRO), one anaplastic (ARO) and one immortalized fetal (TAD-2) cell line have been studied. All of them produced constitutively ICAM-1; its surface expression and specific messenger ribonucleic acid (mRNA) levels were increased significantly by retinoic acid in all except the WRO cell line. ICAM-1 hyperexpression by retinoic acid was time dependent, reversible, and dependent on mRNA and protein synthesis. Furthermore, cytokines, such as interferon-gamma and tumor necrosis factor-alpha, both individually and, to a greater extent, in combination with retinoic acid, increased ICAM-1 surface expression and its mRNA levels. In conclusion, retinoic acid is able to induce ICAM-1 up-regulation via mRNA accumulation in human thyroid carcinoma cell lines.
Blotting, Northern↗
Clinical evaluation of 451 patients with HIV related non-Hodgkin's lymphoma: experience on the Italian cooperative group on AIDS and tumors (GICAT).
We report the clinical experience in 451 patients with HIV related non-Hodgkin's lymphoma (HIV-NHL) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT: Gruppo Italiano Cooperativo AIDS e Tumori), a significant number of them being treated at the Aviano Cancer Center (ACC). High grade histology according to the Working Formulation, stages III-IV and B symptoms were detected in the majority of patients. The median survival was 6 months. Based on the Cox model, three factors appeared to influence survival: advanced stage, treatment received and failure to obtain complete remission (CR). In another study aimed at comparing between chemotherapy with or without G-CSF it was shown that G-CSF significantly reduced white blood cells (WBC) nadir duration, the mean delays between cycles, the mean hospitalization time for toxicity per patient treated, without increasing significantly the overall costs. Furthermore, of 77 GICAT patients treated at the ACC with (group A) or without (group B) long-lasting CR, performance status and the mean CD4+ cell count at time of NHL diagnosis were the only parameters of statistical relevance. Based on our data HIV related NHLs are highly aggressive malignancies which are associated with a poor prognosis per se, and because of the underlying HIV infection. Long-term survivals and possible cures can, nonetheless, be obtained in a subgroup of patients, who have a better performance status and a less advanced immune dysfunction related to HIV infection.
Acquired Immunodeficiency Syndrome↗
[Air pollution and daily mortality among Milan residents, 1980-89. Preliminary results].
Short term effects of air pollutant levels on daily mortality were studied, using time series approach, in Milan from the year 1980 to 1989. The Poisson regression with autocorrelated residuals was applied. This paper reports preliminary results of the analyses on the association between total daily number of deaths and the 24h mean concentrations, on the same day, for two air pollutants: sulphur dioxide and total suspended particulate. A positive and curvilinear relation (with a logarithmic shape) has been found between total daily mortality and concentration levels for each pollutant. This result confirm a steeper increase in mortality at low concentrations, lower than the international standards in use at the moment.
Air Pollutants↗
[Time series analysis in environmental epidemiology: short-term effects of air pollution on mortality and morbidity].
This work gives an overview of design and analysis of temporal studies using aggregated data in air pollution epidemiology. In the last years time series are often used to study the short-term association between ambient air pollution levels and aggregated health data. Health endpoints are usually daily mortality and/or daily hospital admission data from routine health registers. Air quality data are commonly obtained from one (or a few) fixed site monitoring stations. To detect the temporal association between the time-pattern in air pollution and the time-pattern in health data particular attention needs to be given to the autocorrelation structure, to the seasonality and long term trend in the data, and to the weather variables. Poisson regression with autocorrelated residuals is the suitable statistical method to analyze time studies. Furthermore, the pollutant variable can be analyzed at different lag-times to account for short latency periods in the manifestation of diseases. Studies with temporal aggregated data show the same disadvantages of the ecologic studies, although, in this case, confounding is less of a problem. Temporal studies usually are based on a large database, so that sufficient power can be achieved to detect even weak associations. Finally, the exposure information on subjects is often better characterized by short-term fluctuations in ambient air quality than is the case in geographic aggregations.
Air Pollutants↗
Cloning and functional characterization through antisense mapping of a kappa 3-related opioid receptor.
We have identified a putative opioid receptor from mouse brain (KOR-3), belonging to the G protein-coupled receptor family, that is distinct from the previously cloned mu, delta, and kappa 1 receptors. Assignment of the clone to the opioid receptor family derives from both structural and functional studies. Its predicted amino acid sequence is highly homologous to that of the other opioid receptors, particularly in many of the transmembrane regions, where long stretches are identical to mu, delta, and kappa 1 receptors. Both cyclazocine and nalorphine inhibit cAMP accumulation in COS-7 cells stably expressing the clone. Northern analysis shows that the mRNA is present in brain but not in a number of other organs. Southern analysis suggests a single gene encoding the receptor. A highly selective monoclonal antibody directed against the native kappa 3 receptor recognizes, in Western analysis, the clone expressed in COS-7 cells. The in vitro translation product is also labeled by the antibody. Additional clones reveal the presence of several introns, including one in the second extracellular loop and another in the first transmembrane region. Antisense studies with an oligodeoxynucleotide directed against a region of the second extracellular loop reveal a selective blockade of kappa 3 analgesia in vivo that is not observed with a mismatch oligodeoxynucleotide based upon the antisense sequence. The mu, delta, and kappa 1 analgesia is unaffected by this antisense treatment. Antisense mapping of the clone downstream from the splice site in the first transmembrane region reveals that six different antisense oligodeoxynucleotides all block kappa 3 analgesia. In contrast, only one of an additional six different antisense oligodeoxynucleotides directed at regions upstream from this splice site is effective. This strong demarcation between the two regions raises the possibility of splice variants of the receptor. An additional clone reveals an insert in the 3' untranslated region. In conclusion, the antibody and antisense studies strongly associate KOR-3 with the kappa 3-opioid receptor, although it is not clear whether it is the kappa 3 receptor itself or a splice variant.
Amino Acid Sequence↗
[Possible relationship between childhood malaise and psychiatric disorders in adulthood. Preliminary study on an in-patient sample from the psychiatric unit of the general hospital in Pavia].
The authors report the preliminary data of a study which aims to identify the variables (socio-demographic, clinical and nosographic) which may be used to predict the evolution of psychiatric disorders. A retrospective follow-back study was carried out using the medical records and any other documentation available from medical and psychological centers in order to identify the evolutionary stages of disease and possible pre-disease antecedents. The sample group examined was selected from users attending the Diagnosis and Treatment Psychiatric Unit at Pavia Hospital who were found to have undergone infantile neuropsychiatric outpatient or hospital treatment during childhood. The preliminary phase of the study reports the results of the first 42 cases. The predictive value of the diagnosis made during childhood emerges from an analysis of the results and consequently emphasises the need to orient Infantile Neuropsychiatric structure not only towards diagnosis and care but also, towards a more strictly therapeutic action.
Age Factors↗
The effect of Norplant on glucose metabolism under hyperglycemic hyperinsulinemic conditions.
OBJECTIVES: To assess the impact of a levonorgestrel-releasing implant contraceptive (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA) on glucose metabolism. DESIGN: Prospective evaluation of insulin action and secretion in women under hyperglycemic hyperinsulinemic clamp conditions in the midfollicular phase before and 8 weeks after Norplant placement. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Seven previously normally cycling, nonobese, nondiabetic women participated in the study. INTERVENTIONS: Norplant insertion. MAIN OUTCOME MEASURES: Basal levels of glucose and insulin, as well as glucose-mediated insulin secretion, glucose uptake, and tissue sensitivity to insulin were assessed using the hyperglycemic hyperinsulinemic clamp technique before and after Norplant insertion. RESULTS: Norplant placement did not alter the fasting glucose or insulin levels. However, it was associated with a significant 37% increase in the first phase insulin response from a control level of 51 +/- 8 to 70 +/- 10 microU/mL (conversion factor to SI unit, 7.175), and a significant 48% increase in the second phase insulin response from 60 +/- 5 to 89 +/- 8 microU/mL. In association with this increase in insulin levels after Norplant insertion, total mean body glucose uptake (M) increased from 8.08 +/- 0.91 to 9.53 +/- 0.95 mg/kg per minute. However, when expressed as the total body glucose uptake per unit of insulin, the M:I ratio (a measure of tissue sensitivity to insulin) decreased significantly from a mean of 0.12 +/- 0.02 to 0.10 +/- 0.01 mg/kg per minute per microU/mL. CONCLUSION: Although Norplant insertion does not alter basal glucose and insulin levels, tissue sensitivity to insulin under hyperglycemic hyperinsulinemic conditions is decreased after Norplant insertion.
Adult↗
[A rare mesenchymal tumor of the larynx . Case report and anatomo-clinical features].
Laryngeal chondrosarcoma is an uncommon mesenchymal tumor and in the world literature only 220 cases have been reported. We report in this retrospective examination three cases which age ranged from 54 to 65 years; one was a man and two were women. Two of the tumors arose in the thyroid cartilage, one in the cricoid cartilage. All the cases corresponded to low-grade, well-differentiated chondrosarcomas of the hyaline type (grade I) and two of the patients were alive and free from recurrence or metastasis after 6 and 12 years. One had a recurrence 5 years later with a superior histologic grade (grade II) and died 6 months after laryngectomy from metastatic disease. The AA. discusses the importance of assessing location, size, state of the resection borders, histologic grade and recurrence for the correct evaluation of the neoplasia, for therapeutic and prognostic purposes.
Aged↗
[Anomalous presentation of 2 cases of pulmonary carcinoma: obstructive jaundice and pancreatitis caused by pancreatic metastasis].
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Adrenal Gland Neoplasms↗