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Biomedical subjects

E Gallo

Publications and source records attributed to E Gallo.

At least 55 records · Page 3Linked to original sources

Magnetic resonance imaging and different levels of iron overload in chronic liver disease.

The need for accurate and noninvasive evaluation of liver iron stores prompted us to evaluate the reliability of high-field magnetic resonance imaging equipment in liver patients with low or moderate siderosis, given the poor results obtained using systems operating at low field strength in such cases. Twenty patients with sporadic porphyria cutanea tarda and 28 with comparable chronic liver diseases (chronic hepatitis or cirrhosis) and moderate siderosis were compared with 10 patients with idiopathic or secondary hemochromatosis and 10 healthy controls. Plasma iron profile, ferritin concentration and liver iron concentration, determined with atomic absorption spectroscopy, were matched with the magnetic resonance parameters-namely, transverse relaxation time and the signal intensity for a given proton amount, obtained with equipment operating at a field strength of 1.5 T. Hemochromatosis patients with mean liver iron concentrations of 550 mumol/gm dry wt (vs. 10 mumol of controls) exhibited an impressive reduction in the signal intensity with respect to the other three groups, and this reduction prevented any further comparison with the same porphyria cutanea tarda and chronic liver disease groups, whose liver iron level was twice that of the controls. The signal intensity remained almost unchanged in the latter groups, whereas the transverse relaxation time was significantly reduced. Moreover, correlation with liver iron was significantly inverse in the case of the transverse relaxation time (n = 17, r = 0.62, p = 0.008) and direct in the case of the transverse relaxation rate. The transverse relaxation time values returned to normal in five patients who had completed an iron-depletion program.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Kluyveromyces lactis rDNA as a target for multiple integration by homologous recombination.

Gene targeting to a single chromosomal locus has been extensively used in Saccharomyces cerevisiae. In this study, we have analyzed targeting of a repetitive sequence, the 25S rDNA gene, to the chromosomal rDNA cluster of Kluyveromyces lactis by the use of a replacement vector. We have obtained K. lactis transformants carrying multiple copies of the replacement cassette inserted into the rDNA chromosomal locus. Analysis of several transformants has shown that the number of integrated copies could range from 4 to 40. Moreover, the distribution of integration sites within the rDNA locus was found to differ in most transformants. Single-copy integration at multiple sites, rather than multicopy integration at a very limited number of sites, was found to be the most frequent event. Also, in most transformants, integration sites were distributed at random as well as in an orderly fashion, i.e., in contiguous or alternate rDNA repeats, suggesting that amplification of the integrated sequences, rather than multiple integration events, may account for the copy number of insertions.

Blotting, Northern↗

DSM-III mental disorders in general medical sector: a follow-up and incidence study over a two-year period.

In three general medical settings (general practice, hospital medical wards and emergency rooms) about 20% of the adult attenders had a DSM-III mental disorder, mainly in the area of affective and anxious disorders. Some of these disorders were quite severe. Of those cases reassessed 1 year and 2 years after the first interview, less than a quarter reached a "no-diagnosis status". The chronicity of most cases dependent on the interplay not only of either relapse or duration of the main disorder but also of comorbidity and incidence of new disorders. A high incidence of more transient disorders in subjects who were well at first assessment was also found.

Adult↗

Expression of cytochrome P450 in yeast after different chemical treatments.

In Saccharomyces cerevisiae a number of chemical agents induce synthesis of cytochrome P450. A cytochrome P450 gene has been well characterized in this yeast: CYP51, which codes for a constitutive enzyme involved in the 14 alpha-demethylation of lanosterol, a key step in the biosynthesis of ergosterol. In this work, we have analysed the level of transcription of the CYP51 gene in correlation with cytochrome P450 enzymatic activity after treatment with several chemical agents known to interact with cytochrome P450. Using as a probe a DNA fragment whose identity to the CYP51 gene was established by sequence analysis and mapping on chromosome VIII, a unique RNA species was observed in all treatment samples. The increased level found for this transcript in cells treated with ethanol, 20% glucose, phenobarbital or 5-methoxypsoralen correlates with the levels of induction in cytochrome P450 enzymatic activity measured in cells grown under the same conditions, indicating that induction of cytochrome P450 by these treatments is regulated at the transcriptional level.

7-Alkoxycoumarin O-Dealkylase↗

MACOP-B treatment in diffuse large-cell lymphoma: identification of prognostic groups in an Italian multicenter study.

PURPOSE: The prognosis of advanced-stage diffuse large-cell lymphoma (DLCL) has improved with the use of the third-generation regimens such as methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). However, different results have been reported. Therefore, we started a cooperative study to confirm the efficacy of MACOP-B. An analysis of prognostic factors was also performed to identify poor-prognosis patients. PATIENTS AND METHODS: Between June 1986 and March 1989, 180 patients with advanced-stage DLCL were treated with MACOP-B. MACOP-B was given according to the original scheme. Numerous clinical features possibly predictive for complete response (CR), disease-free survival (DFS), and survival were analyzed in univariate and multivariate analyses. RESULTS: One hundred twenty-seven patients (71%) achieved a complete remission, 20 (11%) achieved a partial remission, 24 (13%) had unchanged or progressive disease, and nine (5%) died due to toxicity. With a median follow-up of 28 months, 71% of 127 CRs remain in first remission. Predicted 3-year survival for all 180 patients is 60%, and 3-year DFS for the 127 CRs is 67%. Overall toxicity was acceptable, with mucositis being the most frequent severe side effect. A multivariate regression analysis identified lactate dehydrogenase (LDH) level, bone marrow involvement, and tumor burden as independent risk factors for survival. These factors were also important for achievement of remission and DFS and allowed us to identify three distinct risk groups of patients with good, intermediate, and poor prognosis, with 3-year survival rates of 80%, 59%, and %29, respectively. CONCLUSIONS: These results confirm the effectiveness of MACOP-B in advanced-stage DLCL at low or intermediate risk; however, high-risk patients are in urgent need of new therapeutic approaches. A better definition of prognostic features would allow a more reliable comparison of different treatment regimens, as well as an effective tailoring of therapy by prognostic groups.

Adolescent↗

Contact sensitivity to oxazolone in the chicken: evidence for Arthus type hypersensitivity of the cutaneous reaction.

Cutaneous hypersensitivity reaction can be induced in chickens by skin painting with oxazolone, 33 mg/Kg of body weight (KBW). The B cell contribution to the generation of the cutaneous reaction has been a matter of controversy. In an attempt to characterize this reaction we placed special interest on the possibility that the nature of this reaction could be Arthus type hypersensitivity. From the kinetics study on the cutaneous hypersensitivity after challenge with oxazolonated egg-albumin (EA-OX) it was excluded that the nature of this reaction could be delayed type hypersensitivity. Immune sera transfer experiments demonstrated that the cutaneous reaction was antibody dependent. Serum anti-oxazolone antibody titers in sensitized chickens were assayed by antiglobulin haemagglutination, using oxazolone coupled sheep erythrocytes (OX-SRBC). High titres of IgG were found in contact sensitized chickens. Furthermore this cutaneous reaction was characterized by neutrophils, inflammatory edema, rare thrombotic occlusion of small venules and on absence of monocytes. The utilization of complete Freunds' adjuvant (CFA) given at sensitization demonstrated that CFA enhanced oxazolone antibodies in the sera of immunized chickens without a correlated increase in the intensity of the cutaneous reaction to EA-OX. Animals sensitized to oxazolone (33 mg/KBW) without CFA and challenged intravenously seven days later with oxazolone coupled to autologous chicken red blood cells (OX-CRBC) died from anaphylactic shock; instead animals with the same treatment but with CFA given at sensitization did not die from anaphylactic shock. Taken collectively it was concluded that the cutaneous reaction to oxazolone in the chicken can be categorized as Arthus hypersensitivity. The relationship between cutaneous Arthus reaction and anaphylactic shock in chickens sensitized to oxazolone is discussed.

Anaphylaxis↗

[Not Available].

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Community Medicine↗

Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation.

We analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU-L) in liquid culture in the presence of five potential differentiation inducers: trans-retinoic acid, 1,25-dihydroxy vitamin D3, interferon gamma, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), used singly and with two combined. The culture medium contained either fetal bovine or human serum from normal donors. CFU-L recovery after 7 days was compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15 displayed greater than 50% CFU-L reduction in response to one or more inducers. In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction test, an increase in the percentage of functionally mature (NBT-positive) cells was detected. The combination of retinoic acid with interferon gamma was most effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M-CSF displayed either inhibitory or stimulatory activity in different AML cases. The type of serum employed generally did not affect the response to inducers of differentiation. No significant inhibition of the recovery of granulocyte-macrophage colony-forming units was determined by the five inducers in experiments with three normal bone marrow samples. Our experiments indicate that biological differentiation inducers can reduce AML CFU-L self-renewal and increase the proportion of differentiated cells at concentrations that do not affect normal myelopoiesis and could be achieved during treatments in vivo.

Acute Disease↗

Human recombinant stem cell factor stimulates in vitro proliferation of acute myeloid leukemia cells and expands the clonogenic cell pool.

Stem cell factor (SCF) is a new growth factor acting on early hematopoietic progenitor and stem cells. In our experiments human recombinant SCF stimulated short-term proliferation of accessory cell-depleted acute myeloid leukemia (AML) cells in 13/14 cases, as determined by 3H-thymidine (3H-TdR) incorporation and cell counts. Stimulatory activity was significantly greater than in the presence of GM-CSF and was comparable to that of granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), and 5637 cell line supernatant (SN). Conversely, the ability of SCF to induce primary colony formation by AML clonogenic cells (CFU-L) was lower than that of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 5637 SN in all but four cases. However, SCF potentiated the stimulatory effect of GM-CSF, G-CSF, and IL-3 on both 3H-TdR incorporation and colony formation. In a 7-day liquid culture SCF enhanced CFU-L recovery in all cases to a significantly greater extent than the other growth factors. A further increment was obtained by combinations of SCF with GM-CSF, G-CSF, or IL-3, and this was significantly more effective than 5637 SN. SCF did not induce leukemic cell differentiation. Human recombinant SCF is therefore highly efficient in stimulating AML cell proliferation and expanding the CFU-L pool. It was not, however, able to support long-term growth of AML cells (beyond 2-7 weeks) in five cases tested.

Antigens, Differentiation, Myelomonocytic↗

Doppler flowmetry and the diagnosis of breast lumps.

The aim of the study was to ascertain the reliability of a Doppler signal in the diagnosis of breast cancer. Computerized blood flow analysis was performed on 117 patients who presented with a breast lump at the Division of Diagnostic Oncology of the Istituto Nazionale Tumori of Milan. The values of systolic peak and diastolic frequency were evaluated in relation to the histologic diagnosis. Ten patients had a spontaneous regression of the lump and were excluded from the study. The number of evaluable cases with histologic confirmation was 107: 69 carcinomas and 38 benign lesions. Systolic peak values for the 69 carcinomas ranged from 1500 to 7400 Hz, with a mean value of 3243.4 Hz; diastolic frequency ranged from 200 to 3700 Hz, with mean value of 1413.9 Hz. No diagnostic signals were found in 4 breast cancers (false negatives). Twenty-three of 38 benign lesions (60.5%) and 65 of 69 malignant nodes (94.2%) were correctly diagnosed. The Doppler signal with computerized spectral analysis in addition to more specific ultrasonographic parameters could be considered a useful tool in the diagnosis of breast cancer.

Adult↗

[Role of magnetic resonance in the diagnosis of cryptorchidism].

The paper reports the authors' personal experience regarding the use of magnetic resonance imaging in the diagnosis of cryptorchidism. The result of the study of 13 patients with non-palpable gonads, who all underwent surgical confirmation (with positive outcome in 66% of cases), encourage the use of this non-invasive method with a high anatomic resolution, which can be used to diagnose both the site, dimensions and possible structural alterations of the gonad.

Cryptorchidism↗

CD9 antigen on acute non-lymphoid leukemia cells: preferential expression by promyelocytic (M3) subtype.

A monoclonal antibody (S17-12), previously described to recognize subsets of myelomonocytic cells, is demonstrated to bind CD9 antigen, a surface marker of B-cell precursors, platelets and several non-hematopoietic tissues. The proportion of S17-12, CD9-positive leukemic cells was determined in 102 patients with acute non-lymphocytic leukemia. It was found to be above 75% in 14/22 M3 cases (including 3/3 of microgranular variant) and only in 1/80 cases of different FAB subtype. Complete reactivity (greater than 95%) of leukemic clonogenic cells with CD9 MoAB was restricted to 4/18 M3 cases. Therefore, a high proportion of CD9-positive cells seems to be peculiar to M3 cases. This may help in the diagnosis of cases that lack typical morphological features.

Antibodies, Monoclonal↗

Peripheral blood expansion of early progenitor cells after high-dose cyclophosphamide and rhGM-CSF.

In 20 patients with non-Hodgkin lymphoma or breast cancer, high-dose cyclophosphamide induced, during the post-nadir period of rapid leucocyte recovery, on median day 19 about a 30-fold increase in the peak concentration of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) colony-forming cells, and an even higher increase in the more immature pluripotent progenitors (CFU-Mix, 72-fold). After infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), peak concentration was reached earlier (median day 15) and with further enhancements (159, 116 and 283-fold respectively, in the number of CFU-GM, BFU-E and CFU-Mix). Most CFU-GM were immature, lacking the differentiation antigen CD15, and gave rise to large myeloid colonies, reflecting a high proliferative capacity of the founder cells. Very immature maphosphamide-resistant progenitors were detectable. The marked expansion in the circulating pool was predictable and reliable, allowing harvesting, after two or three leukaphereses, of sufficient haematopoietic progenitors for autologous bone-marrow reconstitution.

Adult↗

Liver iron overload and desferrioxamine treatment of porphyria cutanea tarda.

The aim of this paper is to evaluate invasive and non-invasive indices of iron store and compare the effectiveness of different ferrodepletive protocols in 150 patients with porphyria cutanea tarda (PCT). Iron removal was performed either by intensive phlebotomy (22 cases) or slow subcutaneous and high intravenous doses of desferrioxamine (18 and 5 cases, respectively), and several laboratory parameters were studied; among these, oligo-elements and urinary porphyrins (detected by HPLC) were taken into account before and after the treatments. Serum iron, transferrin saturation, ferritin (RIA) and nuclear magnetic resonance results were compared with invasive findings in order to detect the metal deposition in liver tissue (atomic absorption concentration, optic or electron-microscopic detection). Liver iron overload was observed in 95% of cases. Full normalization of the disease took place by all the treatments, even if it required slightly more time in the phlebotomy group. We may conclude that ferrodepletive treatments are highly effective in PCT and, considering the fact that siderosis and liver damage always accompany the disease, these treatments are proposed as first choice in such cases.

Bloodletting↗

Carrier detection for hemophilia B: evaluation of multiple polymorphic sites.

DNA analysis was performed in families with hemophilia B. Restriction fragment length polymorphisms (RFLPs) produced by endonucleases Taql, Xmnl, and Ddel were studied by two factor IX genomic probes, F9(VIII) and F9(XIII). Fifty-seven subjects from ten families were investigated; of them, 31 were carriers (11 obligate and 20 potential). Of the potential carriers, ten displayed laboratory features allowing for a phenotypic diagnosis of heterozygosity. Segregation analysis of the markers was informative in 19/20 potential carriers, which belong to nine of the ten studied families. Among the potential carriers, Taql allowed the carriership assessment in 15 (78.9%), Xmnl in 15 (94.7%), and Ddel in two (10.4%). Diagnosis was not possible in one family since a homozygosity in the key individuals with all the employed enzymes (Taql, Xmnl, Ddel, + BamHI) was found. Hemophilia B syndrome in two families likely results from a new mutation. In one family, a first-trimester prenatal diagnosis was performed. The use of RFLP analysis allowed us to improve genetic counseling as compared with the phenotypic evaluation by clotting factor assays. Indeed, evaluation of RFLP increased by 26% the carriership assessment of the potential carriers of the hemophilia B trait.

DNA Probes↗

Role of Na+/H+ exchange in the granulocyte-macrophage colony-stimulating factor-dependent growth of a leukemic cell line.

The growth of the human leukemia cell line AML-193 in a serum-free medium is strictly dependent on the presence of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is one of the major regulators of the myelomonocytic lineage. At present, little is known about the mechanisms by which this growth factor transduces the signal intracellularly. The results of this study demonstrate that GM-CSF needs the operation of a Na+/H+ exchanger, which is located in the plasma membrane of almost every vertebrate cell. In fact, the GM-CSF-dependent proliferation of AML-193 cells is strongly reduced in the presence of the amiloride analog EIPA, a specific inhibitor of the Na+/H+ exchanger. When acidified, AML-193 cells are able to recover the original pHi in a Na(+)-dependent and EIPA-inhibitable way; this demonstrates for the first time the presence of the Na+/H+ exchanger in these cells. Finally, GM-CSF, at doses superimposable to those needed for triggering proliferation, induces in AML-193 cells a sustained alkalinization, which is dependent on a operating Na+/H+ exchange, as it is inhibited by EIPA. These results suggest that GM-CSF, like other growth factors in other cell systems, exerts its mitogenic activity in AML-193 cells by inducing a Na+/H+ exchanger-mediated rise in pHi.

Amiloride↗

Establishment from an adult leukemic patient of two novel precursor B cell lines with different growth modality.

Two novel cell lines, PC-53 and PC-53A were established from an adult ALL patient, at third relapse and in the terminal accelerated phase respectively. Both lines displayed the phenotype of B-cell precursors (CD19+, CD38+, CD20-, cytoplasmic-mu-, immunoglobulin gene rearrangement), identical to the freshly isolated blast cells. Chromosomal analysis showed a prominent 45-XX karyotype, including three marker chromosomes. No chromosome 8 abnormalities were detectable, consistently with a non-rearranged c-myc locus. Both cell lines were EBV-negative. Growth stimulation by autologous supernatant was observed for PC-53 cells during the first 4 months in culture, whereas it was much less evident for PC-53A cells. Thus, PC-53 and PC-53A cells represent a useful tool to investigate the mechanisms involved in the clonal expansion of B-cell precursors.

Adult↗

[Role of anterior scalene muscle hypertrophy in thoracic outlet syndrome].

A case of hypertrophic anterior scalene muscle surgically treated is reported. The patient suffered from upper limb intermittent claudication at any sustained upper extremity activity such as lifting a weight or opening and closing the hand with the arm abducted. Doppler and angiographic study showed significant compression of subclavian artery with hyperabduction and Adson manoeuver. Simple anterior scalenotomy was followed by prompt recovery of symptoms. The results of scalenotomy and other surgical approaches to thoracic outlet syndrome are reviewed in the literature. The most common anomalies of anterior scalene muscle in the TOS are also described. Doppler and arteriographic study in different functional positions are necessary in the evaluation of subclavian artery compression by osseous or muscular structures. In the reported case scalenotomy was at least as effective as 1st rib resection.

Adolescent↗