Biomedical subjects
Publications and source records attributed to G Palumbo.
The levels of flurithromycin in gynecological tissue in 20 female patients were studied after preoperative administration. The tissue flurithromycin levels obtained were comparable to those obtained in serum at 3 and 4 h but were frequently higher than those in serum at 6 and 12 h. Flurithromycin reached the highest concentrations in ovary at 4 h and in endometrium at 6 h.
Fifty-six patients with ALL were investigated for bcr involvement by PCR. Breakpoints were found in 15 patients (26.8%). There were no differences in clinical and hematologic features or the percentages of complete response (CR) between the Ph+ and Ph- cases. The duration of CR was 6 and 8 months, respectively. In 7/9 Ph1 relapsed ALL we observed increased expression of myeloid markers and 2/9 showed a switch of cytotype (Ly-->My). In none of the 13 Ph- relapsed ALL patients did we observe these findings. 7/15 of Ph+ cases expressed P190 and mRNA ela2 and 8/15 patients showed P210, with mRNA b3a2 in 5 and b2a2 in 3, respectively. The percentage of CR was 57% in the P190+ and 87% in the P210+ group. Investigation of more Ph1+ ALL cases treated with a uniform protocol should be performed in the future in order to determine whether any such biological and clinical differences exist.
Bovine and human thyroglobulin show two closely migrating bands in reducing SDS-PAGE. Limited digestion with chymotrypsin, trypsin and thermolysin converted the slower band of the doublet into a peptide identical to the faster band, with an apparent mass of 270 kDa, in both species. The starting point of the faster band of the doublet was established at Ileu 520 with native bovine Tg and at Ser 503 with native human Tg, and at Ser 503 and Ser 504 with chymotrypsin-digested bovine and human Tg, respectively. These data explain the electrophoretic heterogeneity of thyroglobulin and unveil a region highly susceptible to proteolysis at about 500 residues from the NH2-terminus of the molecule.
A 44-week clinical study was carried out on a large sample of the Italian infant population to measure the incidence of diaper (napkin) dermatitis and to identify the factors related to the development of diaper dermatitis. Factors such as age, sex, the presence of atopic dermatitis, the general state of health of the child, the use of drugs and the type of diaper used were recorded. At the end of the test, 2169 clinical dermatological examinations were performed. The frequency of episodes of diaper dermatitis was 15.2%. Statistical correlations between diaper dermatitis and age, presence of atopic dermatitis, and health conditions were found.
Previous studies have shown that calcium-antagonists may reduce the development of experimental atherosclerosis, and that nifedipine may slow progression of coronary atherosclerosis in man. The mechanisms responsible for this effect are still unclear. It has been recently proposed that oxygen-free radicals can induce peroxidation of human low-density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemical modified LDL are internalized by macrophages via specific cell surface receptor that was termed the scavenger receptor, and could induce foam cells transformation in vivo. Previous studies on other systems have shown that calcium-antagonists may effectively inhibit oxygen radical-induced lipid peroxidation. These drugs, though differing widely in their chemical structure, are lipophilic to various degrees and presumably would concentrate in the lipid domain of the phospholipid-rich membranes. Therefore, the aim of the present study was to investigate whether calcium-channel blockers may reduce human LDL peroxidation. Purified human LDL were exposed to oxygen radicals generated by xanthine-xanthine oxidase (18 hours) after a pre-incubation (30 min) in presence of different concentrations of nifedipine, diltiazem and verapamil. Peroxidation was measured from malonyldialdehyde production. The results show that calcium-antagonists prevent LDL peroxidation. Thus, calcium-antagonists may reduce peroxidation of human LDL in vitro, at clinically relevant concentrations. These data suggest that reduced formation of atherogenic peroxidized LDL may be an additional mechanism for the anti-atherosclerotic effects of calcium-antagonists in vivo.
Ultraviolet irradiation of the [3H]colchicine-tubulin complex leads to direct photolabeling of tubulin with low but practicable efficiency. The bulk (70% to greater than 90%) of the labeling occurs on beta-tubulin and appears early after irradiation, whereas alpha-tubulin is labeled later. The labeling ratio of beta-tubulin to alpha-tubulin (beta/alpha ratio) is reduced by prolonged incubation, prolonged irradiation, urea, high ionic strength, the use of aged tubulin, dilution of tubulin, or large concentrations of colchicine or podophyllotoxin. Glycerol increases the beta/alpha ratio. Limited data with [3H]podophyllotoxin show that it covalently bound with a similar beta/alpha distribution. Vinblastine, on the other hand, exhibits preferential attachment to alpha-tubulin. The possibilities that colchicine binds at the interface between alpha-tubulin and beta-tubulin, that the drug spans this interface, and that both subunits may contribute to the binding site are suggested.
A high-performance liquid chromatographic method for the quantification of rufloxacin in human serum and urine has been developed and validated. The compounds, rufloxacin and internal standard, are extracted from buffered serum and urine using dichloromethane. They are then separated on an anion-exchange column using 0.05 M phosphate buffer-acetonitrile (80:20, v/v). The eluate is quantified by measuring the ultraviolet absorbance at 296 nm. The lower limit of detection for the analyte is 0.1 microgram/ml in serum and 0.05 micrograms/ml in urine. The method is linear from 0.3 to 10 micrograms/ml for serum and 0.1 to 10 micrograms/ml for urine. The method has been applied in a pharmacokinetic study in volunteers.
Cardiopulmonary By-Pass (CPB) Surgery may at times induce a haemostatic defect, at present not too well understood, causing severe bleeding from the operative site and chest tube drain. We present here some data on antigen increase in tissue Plasminogen Activator (tPA) and D 2 Dimer (D2D) detected during CPB and apparently not compensated by enhanced Plasminogen Activator Inhibitor type 1 (PAI 1) activity. tPA concentration (antigenic) ranged around 6.15 ng/ml (SD 5.6) before thoracotomy and 5.8 g/ml (SD 4.74) 5-10 minutes after a heparin 250 IU/Kg bolus injection. During CPB, tPA increased to 20.34 ng/ml (SD 9.17) before protamine infusion, and 16.93 ng/ml (SD 8.13) after heparin neutralization. As the D2D went up to 2000-4000 ng/ml (before/after protamine) and it was not correlated by fibrinogen consumption or FDP production, we find these observations suggestive of fibrin-dependent fibrinolytic activity, as an acquired haemostatic defect developed during CPB.
The present study was designed to examine the possibility that individual differences in heartbeat perception and instructions to control heart rate (HR) may influence the acquisition of voluntary control. Good (n = 20) and poor (n = 20) perceivers of cardiac activity were selected on the basis of their performance according to Whitehead et al. (1977) heartbeat discrimination procedure. Measures of state and trait anxiety (the State-Trait Anxiety Inventory Form X-1 and Form X-2) and Tellegen's Absorption Scale (TAS) were used to assess emotionality and absorptive ability. Good and poor heartbeat perceivers (a) were given non-motivating instructions to try to either increase or decrease their heart rate (HR) with, or (b) without the use of HR-feedback, and (c) were given motivating instructions to try to either increase or decrease their HR with, or (d) without HR-feedback. Heart rate, skin conductance (SC), and EMG activity were monitored. Subjects were also requested to indicate the cognitive strategies used during their HR control training. No relationship between heartbeat perception and state-trait anxiety measures was found. The results did not support the idea that individual differences in heartbeat perception are related to individual differences in HR-control. They did indicate, however, that motivating instructions improve the capacity to increase or decrease HR. Subjects were able to voluntarily increase or decrease their HRs with or without a feedback signal. However, more pronounced HR increases were obtained in the feedback as compared with the no-feedback condition. SC and EMG activity were in accordance with arousal levels demanded by HR decrease and increase tasks. Subjects used cognitive strategies concerning activation responses during HR-increase and relaxation responses during HR-decrease conditions.
A simple, specific, and sensitive high-performance liquid chromatography method has been developed for routine monitoring of the antimicrobial agent rufloxacin in human serum and urine. Serum or urine-spiked with internal standard pipemidic acid, were vortex-mixed for 2 min with dichloromethane at pH 7.4. The evaporated extract was dissolved in 0.05 M NaOH. The mobile phase consisted of orthophosphoric acid, tetrabutylammonium iodide, and methanol. Drugs were resolved at ambient temperature on a 10 micron Viosfer LC-RP-18 column (250 x 4.6 mm I.D.) equipped with a guard column. Flow rate was 1.8 ml/min, and monitoring was performed at 295 nm. The calibration curve was linear from 0.1 to 10 micrograms/ml for human serum and from 0.05 to 10 micrograms/ml for urine. Retention times were 3.1 and 6.3 min for internal standard and rufloxacin. The detection limit of rufloxacin was 0.05 microgram/ml for human serum and 0.03 microgram/ml for urine. No interference from other commonly administered drugs or endogenous substances was observed. The assay demonstrated sufficient sensitivity and specificity for the study of the pharmacokinetics of rufloxacin in humans.
Low-density lipoproteins (LDL) oxidized by oxygen radicals (OR) are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and may induce foam cells transformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2). It is unknown whether LDL are modified via direct lipid oxidation by OR, or whether LDL are subsequently oxidized via chain reactions after initial OR attack. To distinguish between these 2 mechanisms, LDL were exposed to OR formed by xanthine/xanthine oxidase (X/XO). Peroxidation was measured from malonyldialdehyde (MDA) levels. Parallel experiments were performed in presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), or the hydrogen peroxide scavenger catalase (CAT; 1000 U/ml), or by adding the chain-reaction inhibitor butylhydroxytoluene (BHT; 1 mM) at selected time points. SOD, but not CAT prevented LDL peroxidation, indicating an obligatory role for superoxide radicals. Superoxide generation in this model lasts only a few minutes, however, MDA levels continued to increase over several hours. Furthermore, this phenomenon was blocked when BHT was added at various times after X/XO. These data show that LDL peroxidation is triggered by initial OR generation but then involves chain reactions which do not require continuous exposure to OR.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
The gynaecological tissue levels of miocamycin were studied in ten female patients after pre-operative administration. The patients were divided into two groups on the basis of the scheduled sampling time. All the patients received 4200 mg of the drug, divided in 7 tablets of 600 mg each every 8 h, last administration 2 or 3 h before surgery. The tissue levels, obtained by means of the microbiological method (Sarcina lutea 9341), were frequently higher than those obtained in the serum at the same time. Miocamycin reached the highest concentration in the endometrium (2.5 micrograms/g) and the lowest in the vagina (1.1-0.8 micrograms/g).
Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause.
In most highly structured native proteins, as well as in thyroglobulin, the reactivity in vitro of the various tyrosyl residues toward iodine is widely different. The present work demonstrates that of nearly 70 tyrosyl residues present in rat thyroglobulin, there is one, residue number 5 from the NH2-terminal end, which has in vivo the highest affinity toward iodine, being the first one to be iodinated. In fact, when 6-(n-propyl)-2-thiouracil (PTU)-treated, iodine-deficient animals were injected with 125I and killed shortly after, we isolated from thyroid glands poorly iodinated thyroglobulin (about 1 iodine atom/thyroglobulin molecule), nearly 90% of the radioactivity of which was found as monoiodotyrosine. Although CNBr cleavage of this protein gave several fragments after gel electrophoresis only one of these, with apparent mass 27,000 Da, contained 125I. This fragment was isolated and fully characterized. Twelve cycles of automated Edman degradation were performed; the sequence found, i.e. N-I-F-E-X-Q-V-X-A-Q-X-L, indicated that the 27,000-Da fragment is the NH2 terminus of thyroglobulin. This portion of the polypeptide chain contains several tyrosyl residues which may well all be potentially involved in the early iodination of the protein. The observation that the removal of seven amino acids from the NH2 terminus is accompanied (at the fifth step) by the total disappearance of radioactivity in the resulting shortened peptide suggested that the fifth residue was the only one iodinated under these conditions. A second, more quantitative experiment was performed on thyroglobulin obtained from 6-(n-propyl)-2-thiouracil-treated animals whose death was postponed 24 h after the injection of 125I. In this case the radioactivity was found not only in a single CNBr fragment (27,000 Da) but also in other discrete species of lower molecular mass. The mixture of these peptides was subjected to seven steps of manual Edman degradation. Fragments before and after partial degradation were run in parallel on a polyacrylamide gel and the distribution of 125I compared. Besides some change in the background, the two profiles were identical except for the absence of the 27,000-Da species. This proves that all the 125I present in the 27,000-Da species was localized at the fifth residue, the same site at which the hormone molecule is preferentially synthesized under normal conditions. This result is not unexpected and is in accord with the known properties of thyroglobulin which has a polypeptide chain designed for efficient synthesis of the hormone even at low levels of iodination.
In this study of ambulatory patients who had their first visit at the hypertension Unit of the Ospedale San Carlo Borromeo in Milan during the years 1979-1983, we report some data regarding compliance and long-term prognosis of mild hypertension. In these 5 years, 445 mild hypertensives (mean DBP: 103.3 +/- 13.2 mmHg) came to our facilities at least once: of these, 57 (12.9%) have been in constant touch with the outpatient clinic until today; 310 (69.6%) have been lost to follow-up after less than 1 year; 78 (17.5%) had an irregular pattern of attendance with a mean length of follow-up of 3.49 +/- 1.8 years. These data indicate a less than ideal compliance especially for patients who were older, smokers, not married and with no previous pharmacological treatment at the first visit. Index of morbidity and mortality for all causes and for cardiovascular disease and blood pressure control were better, although without reaching statistical significance, in the 57 patients with the best compliance. Altogether our data point to a reevaluation of the approach to the problem of mild hypertension through specialised hospital facilities.
We have cloned a stromal cell from mouse bone marrow selected on the basis of its ability to promote the growth of an Abelson virus-transformed pre-B cell line. These stromal cells have smooth muscle features, and the ultrafiltrate of stromal cell-conditioned medium has proliferative effects on all feeder layer-responsive mouse pre-B cell lines tested, as well as on normal pre-B cells. One of these low MW substances is a protease-resistant factor with an MW of approximately 450 Da which we designate Abelson Growth Promoter (AGP). AGP was initially characterized as an activity which promotes the growth of Abelson virus-transformed mouse pre-B cells, but it also promotes the growth of a ras-transformed pre-B cell line as a single agent and in synergistic fashion with recombinant interleukin (IL) 7. AGP as a single agent has no effect on normal pre-B cells, which have a brisk response to IL-7. In contrast, transformed pre-B cells display a blunted response to IL-7. We propose that AGP plays a role in normal lymphopoiesis by expanding clones of pre-B cells which have been activated by other stromal cell-derived signals, such as IL-7, and directly promotes the growth of nascently transformed pre-B cells.
Explore the source record for details and available documents.