Biomedical subjects

G Cimino

Publications and source records attributed to G Cimino.

At least 91 records · Page 5Linked to original sources

PubMed1994

Polyunsaturated-fatty-acid oxidation in Hydra: regioselectivity, substrate-dependent enantioselectivity and possible biological role.

A novel and abundant lipoxygenase-like activity converting cis-eicosa-5,8,11,14-tetraenoic acid (arachidonic acid) into (11R)-hydroxyeicosatetraenoic acid has been recently described in homogenates of the freshwater hydrozoan Hydra vulgaris. In this study, other substrates for this enzyme were selected from the polyunsaturated fatty acids (PUFAs) present in H. vulgaris, and the chemical natures of the hydroperoxy and hydroxy derivatives produced, as well as the activity of some of the latter on hydroid tentacle regeneration, were investigated. The highest conversion among C20 fatty acids was observed for arachidonic acid, and among C18 fatty acids for cis-octadeca-9,12,15- and cis-octadeca-6,9,12-trienoic (alpha- and gamma-linolenic) acids. Cis double bonds on the 10th carbon atom from the aliphatic end of the substrate (e.g. C-9, C-11 and C-13 respectively in C18, C20 and C22 PUFAs) were regiospecifically peroxidized. Conversely, trans-octadeca-9,12-dienoic (linoelaidic) acid was not a substrate for lipoxygenase activity. Enantioselectivity of lipoxygenation depended on the degree of unsaturation of the substrate, with the amount of the R enantiomer increasing when passing, for example, from cis-eicosa-11,14-dienoic to cis-eicosa-5,8,11,14,17-pentaenoic acid. Regiospecific formation of keto acids was observed only when incubating C18 PUFAs. Commercially available hydroxyacids corresponding to the reaction products of some of the most abundant H. vulgaris PUFAs were tested for effects on Hydra tentacle regeneration. An enhancement of average tentacle number, in a fashion depending on the stereochemistry and on the number of double bonds, was found for two compounds, thus suggesting for the 11-lipoxygenase-like enzyme a role in the production of metabolites potentially active in the control of hydroid regenerative processes.

Animals↗

PubMed1994

Some aspects of zinc transport across eel (Anguilla anguilla) red blood cell membranes.

Zinc movement across eel and human red blood cell membranes was measured by atomic absorption spectrophotometry. It was observed that: 1) In human red blood cells zinc uptake is twice as rapid as in fish red blood cells over a temperature range of 10-40 degrees C. The low rate of zinc uptake in eel red blood cell may be simply the side effect of different surface area to volume ratios for the differences in cell size or, it may be due to the low permeability of bicarbonate through the red blood cell membranes. 2) Zinc uptake measured in eel and human red blood cells treated and untreated with external trypsin shows different features. The zinc uptake was reduced by about 40% in treated eel red blood cells with respect to the total uptake of untreated red blood cells. Human red blood cells treated and untreated with trypsin do not show any differences in the amount of zinc transported. 3) In fish red blood cells, zinc uptake in NaNO3 medium is markedly reduced, compared with that measured in NaCl medium. The [Zn2+i slightly increases in the presence of bicarbonate. In human red blood cells in NaNO3 medium the zinc uptake is strongly reduced and the presence of bicarbonate marginally increases the zinc influx. 4) In eel red blood cells there seem to be two independent pathways for zinc uptake: one DIDS-sensitive and the other DIDS-insensitive. DIDS 10 microM inhibits only 64% of the total zinc transported. Increasing the DIDS concentration did not give more inhibition. In human red blood cells only one DIDS-sensitive pathway for zinc transported seems to exist, because, 2, 5 microM DIDS inhibits 97% of zinc uptake.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1994

Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical and biological results of two different regimens.

The use of alpha interferon (alpha IFN) and, more recently, of the purine analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has dramatically improved the prognosis of patients affected by hairy cell leukemia (HCL). DCF has been shown to induce an higher and more durable response rate than IFN, with only moderate myelosuppression and relatively few side effects. In this paper, we report our experience with dCF in a series of 38 HCL patients who had progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha (TNF alpha) levels were also evaluated before, both during and after treatment in order to monitor clinical response. Two schedules of treatment were employed: 23 patients were treated with the EORTC protocol and the following 15 with the NCI regimen. The overall response rate was 94.7%; no significant differences in response rates were observed between the two schedules. In respect to toxicity, we recorded nausea and in two cases a cutaneous rash. Four patients experienced localized herpes zoster and one had a fungal pneumonia. Median overall survival after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC schedule and 77% of those who received the NCI program are currently in CCR at 3 years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment, while no significant changes in serum TNF alpha levels were observed. In our study, dCF was confirmed as an effective agent in HCL, inducing an high response rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Acrofacial dysostoses: review and report of a previously undescribed condition: the autosomal or X-linked dominant Catania form of acrofacial dysostosis.

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders combining defects of craniofacial and limb development. The predominantly preaxial form is called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known as the Genée-Wiedemann or Miller syndrome. The former appears to be about twice as common as the latter with well-documented autosomal dominant and recessive occurrences in both conditions. Only 1 AD occurrence of POADS is known, but 5 sets of sibs are suggestive of AR inheritance. Heterogeneity of apparently nonsyndromal AFD of both types is powerful support for the hypothesis that the AFDs are polytopic field defects arising during blastogenesis. Six other previously described forms of AFD include the AFD syndrome of Kelly et al. (AR), the Rodríguez or Madrid form of AFD (AR or XLR), the Reynolds or Idaho form of AFD (AD), the Arens or Tel Aviv type of AFD (AF?), the presumed AR AFD syndrome of Richieri-Costa et al., and the AD Patterson-Stevenson-Fontaine syndrome. Here we review the AFDs and report on a previously apparently undescribed autosomal or X-linked dominant form of AFD with mental retardation in a Sicilian mother and her 4 sons.

Adolescent↗

PubMed1993

Biosynthesis, structure and biological activity of hydroxyeicosatetraenoic acids in Hydra vulgaris.

Recent reports have suggested the involvement of arachidonic acid (AA) and its metabolites in the control of body pattern, head and tentacle regeneration and bud formation in Hydra spp. Here we describe for the first time the biosynthesis of hydroxyeicosatetraenoic acids (HETEs) in vitro by hydroid cytosolic extracts. Incubation of both unlabelled and tritiated AA with homogenates of Hydra vulgaris led to the conversion of up to 11% of the exogenous fatty acid into mainly two metabolites. These were characterized as 11-hydroperoxyeicosatetraenoic acid (11-HPETE) and 11-HETE by means of a combination of chromatographic, chemical, 1H-n.m.r. and electron-impact m.s. techniques. Trace amounts of 9-HETE and 12-HETE were also found. Analysis of 11-HETE by chiral-phase h.p.l.c. revealed that this metabolite was composed mainly of the R enantiomer. The production of 11-HPETE and 11-HETE was found to be: (1) associated with the cytosolic fraction of Hydra homogenates; (2) dependent on AA concentration, incubation time and protein amount in the homogenates; (3) unaffected by co-incubation with the 5- and 12-lipoxygenase inhibitors, 5,8,11-eicosatriynoic acid and nordihydroguaiaretic acid, the cyclo-oxygenase inhibitor, indomethacin, or the cytochrome P-450 inhibitors, proadifen and methoxalen. These results strongly suggest the presence of a very active (R)-11-lipoxygenase in H. vulgaris. The activity of both R and S enantiomers of synthetic 9-, 11- and 12-HETE and of 'endogenous' 11-HETE was studied on tentacle regeneration and bud formation in decapitated Hydra. Although almost all compounds tested inhibited budding, only endogenous 11-HETE and synthetic (R)-11-HETE significantly enhanced the average number of tentacles, thus suggesting that this eicosanoid might be one of the cellular regulators of regeneration in H. vulgaris.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1993

ALL-1 gene at chromosome 11q23 is consistently altered in acute leukemia of early infancy.

Early infancy (< 1 year of age), massive tumor cell burden, and extremely poor prognosis are characteristic features of a particular subset of childhood acute leukemias (AL). In these cases, chromosome aberrations at the 11q23 band are the most frequently reported cytogenetic abnormalities. We have recently cloned a genetic locus named ALL-1, in which DNA breakpoints are clustered in leukemic patients with 11q23 aberrations. Analysis of the ALL-1 genomic configuration in DNA from 15 infants with AL showed specific ALL-1 rearrangements in 12 cases (80%), including 5 with normal karyotypes. These findings indicate that a consistent genetic defect underlies this particular leukemic subset.

Acute Disease↗

PubMed1993

Photochemical inactivation of cell-associated human immunodeficiency virus in platelet concentrates.

Photochemical decontamination (PCD) of platelet concentrates, with adequate preservation of platelet function, has been shown using 8-methoxypsoralen (8-MOP) and long wavelength UV light (UVA). To further evaluate this technique, models for the inactivation of pathogenic human cell-associated viruses and integrated proviral sequences are required. We have assessed the ability of the PCD technique to inactivate cell-associated human immunodeficiency virus 1 (HIV-1) in platelet concentrates. We correlated PCD inhibition of HIV-1 infectivity with 8-MOP-DNA adduct formation in contaminating nucleated cells, and measured the inhibition of polymerase chain reaction (PCR)-mediated amplification of cellular DNA sequences as a surrogate for inactivation of integrated proviral nucleic acid sequences. After PCD treatment (8-MOP 300 micrograms/mL, UVA 17 mW/cm2) for 60 minutes, 0.5 x 10(6) plaque-forming units (PFU)/mL of cell-associated HIV-1 were inactivated and no virus was detectable by infectivity assay. After 60 minutes of PCD, 15 8-MOP-DNA adducts per 1,000 bp were formed, while in the absence of UVA, no adducts were formed. PCR-mediated amplification of a 242-bp cellular DNA sequence (HLA-DQ-alpha) was inhibited when greater than eight psoralen-DNA adducts per 1,000 bp were present. These studies indicate that high titers of cell-associated HIV-1 in platelet concentrates were inactivated by PCD, and the numbers of 8-MOP-DNA adducts in nucleated cells were sufficient to inhibit amplification of DNA segments that encode for as few as 80 amino acids. Based on the frequency of 8-MOP-DNA adducts, for the 10-kb HIV-1 genome, the probability of an integrated genome without at least one 8-MOP adduct after 60 minutes of PCD was 10(-33).

Blood Component Transfusion↗

PubMed1992

The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene.

The ALL-1 gene located at human chromosome 11 band q23 is rearranged in acute leukemias with interstitial deletions or reciprocal translocations between this region and chromosomes 1, 4, 6, 9, 10, or 19. The gene spans approximately 100 kb of DNA and contains at least 21 exons. It encodes a protein of more than 3910 amino acids containing three regions with homology to sequences within the Drosophila trithorax gene, including cysteine-rich regions that can be folded into six zinc finger-like domains. The breakpoint cluster region within ALL-1 spans 8 kb and encompasses several small exons, most of which begin in the same phase of the open reading frame. The t(4;11) chromosome translocation results in two reciprocal fusion products coding for chimeric proteins derived from ALL-1 and from a gene on chromosome 4. This suggests that each 11q23 abnormality gives rise to a specific oncogenic fusion protein.

Amino Acid Sequence↗

PubMed1992

The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase.

Chromosomal region 11q23 is frequently rearranged in acute lymphocytic leukemias (ALLs) and in acute myeloid leukemias (AMLs), mostly in reciprocal exchanges with various translocation partners. The most common of these translocations is t(4;11)(q21;q23). It is present in approximately 10% of ALL patients, most frequently in very young children. We have recently cloned a region of chromosome 11, the ALL-1 locus, found to be rearranged in malignant cells from patients with the t(4;11), t(9;11), t(11;19), t(1;11), t(6;11), t(10;11), and del(11q23) chromosomal abnormalities. Here we report the cloning and characterization of chromosomal breakpoints from leukemic cells with t(4;11) aberrations. The breakpoints cluster in regions of 7-8 kilobases on both chromosomes 4 and 11. The presence of heptamer- and nonamer-like sequences at the sites of breakage suggests that the VDJ recombinase utilized for immunoglobulin gene rearrangement is also directly involved in these translocations. We also show that leukemic cells with t(4;11) express altered RNAs transcribed from the derivative chromosomes 11 and 4.

Acute Disease↗

PubMed1992

An altered 11-kilobase transcript in leukemic cell lines with the t(4;11)(q21;q23) chromosome translocation.

The 11q23 chromosome band is frequently associated with chromosomal aberrations in human leukemias. We have previously cloned a DNA fragment derived from chromosome 11 which could be used as a probe to detect rearrangements in DNAs from the leukemic cells of patients with the t(4;11), t(9;11), and t(11;19) translocations. In this study we now show that the same probe detects DNA rearrangements in malignant cells from patients with the t(1;11), t(6;11), t(10;11), and del (11q23) chromosomal abnormalities. A second probe obtained from a region located centrometric to the breakpoint cluster detects major and minor transcripts of 12.5 and 11.5 kilobases, respectively, in all cell lines examined. The same probe identifies an altered 11-kilobase RNA in all three independent cell lines with the t(4;11)(q21;q23) chromosome translocation.

Chromosomes, Human, Pair 11↗

PubMed1992

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin.

The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Selected biological activities of saraines.

1. The Mediterranean sponge Reniera sarai, Pulitzeri-Finali, 1969 (Demospongiae: Haploscleridae: Renieridae) possesses in large amounts a series of unprecedented polycyclic alkaloids, saraines 1-3 and saraines A-C. 2. The structural peculiarities of saraines, their chemical-physical characteristics, along with their relevant abundance in the sponge, prompted a study aimed at investigating their biological properties. 3. Saraines were assayed for their cytotoxic, antibacterial, insecticidal and potential antitumoral activities. These results, along with the growth inhibition of fertilized sea urchin eggs, are reported.

Aedes↗

PubMed1992

Chemotherapy versus radiotherapy in early-stage Hodgkin's disease: evidence of a more difficult rescue for patients relapsed after chemotherapy.

Six cycles of mechloretamine, vincristine, procarbazine and prednisone (MOPP) chemotherapy were randomly compared with extended field radiotherapy (RT) in 89 adult patients with pathological stage I-II A Hodgkin's disease (HD). 45 patients received RT and 44 were treated with MOPP. Complete remission (CR) was obtained in all patients in the RT group and in 40 of 44 in the MOPP group. 12 patients relapsed in both groups. 10 out of 44 patients treated with MOPP died of HD, compared with only 2 in the RT group. 3 more patients died in the MOPP group following the occurrence of second cancers. 11 out of the 12 (96%) patients relapsing after RT achieved a second CR, compared with 6 out of the 12 (50%) patients relapsing after MOPP. Analysis of the response rate with salvage treatment, shows that, of the 12 patients who relapsed after MOPP, the pattern of relapse might predict the likelihood of achieving a second CR, whereas in the RT group a second CR was achieved regardless of the characteristics of relapse. Survival probability for relapsing patients at 80 months calculated from relapse was 85% in the RT group and 15% in the MOPP group (P = 0.02). With a median follow-up of more than 8 years, the overall survival of patients was significantly better for RT compared with MOPP; 93 and 56%, respectively (P < 0.001). On the basis of these results we conclude that, to date, RT alone remains the treatment of choice for adult patients with early-stage HD with favourable prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Ichthyotoxic diterpenoids from the Cantabrian nudibranch Chromodoris luteorosea.

Five spongian diterpenoids 2, 3, 6-8, previously found in sponges and nudibranchs from very distinct geographical areas, have been isolated from the Cantabrian nudibranch Chromodoris luteorosea. The terpenoids are mainly localized along the border of the mantle of the mollusk. All the diterpenoids are toxic to Gambusia affinis.

Animals↗

PubMed1992

4-acetylaplykurodin B and aplykurodinone B, two ichthyotoxic degraded sterols from the Mediterranean mollusk Aplysia fasciata.

Two ichthyotoxic lactones, 4-acetylaplykurodin B [1] and aplykurodinone B [2], were isolated from the external parts of the body of the mollusk Aplysia fasciata. Their structures, determined by spectroscopic and chemical means, are closely related to aplykurodin B [3] previously isolated from Aplysia kurodai. The interconversion of delta- and gamma-lactones in the aplykurodin derivatives has been also investigated.

Animals↗

PubMed1992

Single daily dose ceftriaxone plus amikacin treatment of febrile episodes in neutropenic patients attending day hospital for hematologic malignancies.

Once-a-day ceftriaxone and amikacin was administered in case of fever to 46 neutropenic patients attending day hospital for hematologic malignancies. All patients were admitted to a short-term ward for infective complications, but were discharged in the event of prompt disappearance of fever and of clinical signs of infection continuing their therapy either by daily reporting to the hospital, or at home. Response to the initial empiric therapy was obtained in 37 cases (76%). Twenty-four patients who promptly responded to therapy completed their treatment on an outpatient basis, their mean number of days of hospitalization being reduced to 4.6 versus a mean of 9.6 days in the overall patient population being considered. Since the outpatient treatment accounted for 21% of the antibiotic therapy administered, the above treatment may result in cost containment and better quality of life for patients, provided that these data are confirmed by prospective randomized studies.

Adolescent↗

PubMed1992

Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.

PURPOSE: To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS: From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS: All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION: We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.

Actuarial Analysis↗

PubMed1992

[Not Available].

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France↗