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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 613 records · Page 34Linked to original sources
PubMed1985

The effects of cellular glutathione elevation on the oxygen enhancement ratio.

The radiation responses at various oxygen tensions were evaluated in V79 Chinese hamster cells under conditions where their nonprotein thiols, primarily glutathione (GSH), were elevated by 2-oxothiazolidine-4-carboxylate (OTZ). OTZ, when cleaved by intracellular oxoprolinase, provides the cell with cysteine which stimulates GSH synthesis. A 2-hr pretreatment with 10 mM OTZ elevated GSH to 200% of controls. This elevation in GSH offered no protection to aerated cells; however, for O2 tensions less than or equal to 40,000 ppm modest protection was observed as evidenced by an increase in oxygen enhancement ratio. GSH elevation afforded maximal protection between 1000 and 10,000 ppm O2; however, the extent of protection was relatively small (protection factor = 1.3).

Animals↗
PubMed1985

Depletion of cellular glutathione by exogenous spermine in V79 cells: implications for spermine-induced hyperthermic sensitization.

The relationship between spermine-induced thermosensitization and modulation in the cellular redox state as measured by glutathione levels was studied using Chinese hamster V79 cells. Marked cellular glutathione depletion was observed for cells treated with exogenous 1 mM spermine at 37 degrees C or 43 degrees C. Glutathione depletion and thermal sensitization by spermine were found to be cell density dependent with maximum depletion and sensitization observed at low cell densities. These findings are discussed in the context that treatment of cells with exogenous polyamines such as spermine can result in cellular oxidative stress which may in part contribute to spermine-induced thermal sensitization.

Animals↗
PubMed1985

[The FG syndrome (McK 30545). Description of 2 cases with subaortic stenosis].

This paper reports on two brothers affected by FG syndrome (a rare X-linked syndrome with multiple congenital anomalies and mental retardation) and subvalvular aortic stenosis of the discrete type. This is a previously unrecognized association. The FG syndrome was firstly described by Opitz and Kaveggia in 1974. Nearly 20 cases have been reported: congenital heart diseases previously reported are atrial septal defect, ventricular septal defect and hypoplastic left heart. The clinical appearance of the two cases we have observed was that of mental retardation and typical features including abnormal facies (dolicocephaly, frontal prominence, poorly modeled auricles, micrognathia, prominent lower lip and lack of expression), anteriorly displaced anal opening, clinodactyly, great broad toes. A chromosome study showed a normal 46 XY constitution. Discrete subvalvular aortic stenosis was diagnosed by typical physical and echocardiographic findings.

Abnormalities, Multiple↗
PubMed1985

Potentiation and protection of doxorubicin cytotoxicity by cellular glutathione modulation.

One of the proposed mechanisms of doxorubicin cytotoxicity is generation of activated oxygen species, all of which are either free radical or potentially free radical species. Glutathione is an intracellular sulfhydryl-containing tripeptide that is known to detoxify free radicals and the damage they produce. The cytotoxicity of doxorubicin was evaluated following treatment with agents that will either elevate intracellular glutathione (2-oxothiazolidine-4-carboxylate) or deplete intracellular glutathione levels correlate with doxorubicin cytotoxicity, ie, elevated glutathione provides protection and decreased glutathione levels increase cytotoxicity. These results are discussed in the context of cardiac toxicity as well as enhancing tumor cell kill with doxorubicin.

Animals↗
PubMed1984

[Projections to the supraoptic and paraventricular nuclei studied in the rat by means of retrograde fluorescent tracers (fast blue, nuclear yellow)].

Afferent projections into rat supraoptic nucleus (SO) and paraventricular nucleus (PVH) were studied with two fluorescent retrograde neuronal tracers: Nuclear Yellow (NY) and Fast Blue (FB). FB labeled cells were found into paraolfactory area (ACB), basolateral amygdaloid nucleus (ABL), lateral hypothalamus (LH), ventromedial nucleus (VMH) and dorsomedial hypothalamic)nucleus (DMH), tegmental nucleus of the pons (TPO). NY labeled cells were found into posterior hypothalamus (PH), dorsal raphe nucleus (DR) and tegmental nucleus of the pons (TPO). Few double-labeled neurons were found into TPO. The finding of double labeled neurons in the TPO is of particular interest. This latter nucleus is classically connected to the cerebellum trough the olivary nucleus and can serve as liaison for transmission of messages, e.g. vestibular, regarding spacial position variations. We can conclude affirming that quite a lot of informations of diverse nature converges on the SO and PVH nuclei that by efferent pathways may regulate hypothalamic neurosecretion, thus modifying the animal's behaviour response to different external stimuli.

Afferent Pathways↗
PubMed1984

Metabolic studies of mammalian cells by 31P-NMR using a continuous perfusion technique.

Levels of ATP and Pi in metabolically active Chinese hamster lung fibroblasts were monitored noninvasively by 31P-NMR over many hours and under a variety of conditions. The cells were embedded in a matrix of agarose gel in the form of fine threads which were continuously perfused in a standard NMR tube. The small diameter of the thread allows rapid diffusion of metabolites and drugs into the cells. The changes in ATP and Pi levels were followed as a function of time in response to perfusion with a glucose-containing medium, with isotonic saline and with a medium containing 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation. This gel-thread perfusion method should enable routine NMR studies of cellular metabolism, and may have other potential biological applications.

2,4-Dinitrophenol↗
PubMed1984

Nondisjunction induced in mouse spermatogenesis by chloral hydrate, a metabolite of trichloroethylene.

The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evaluated by cytogenetic observations of mouse secondary spermatocytes after ip treatment with 82.7, 165.4, or 413.5 mg/kg bw. Hyper-haploid metaphases have been scored to determine whether previous observations in various nonmammalian organisms about an effect of this drug on the mitotic spindle could be confirmed in mice. At each dose, the frequencies of hyper-haploid cells have been estimated to assess the response of pachytene, preleptotene, premeiotic, and staminal gonial cells. Significant increases above the control value have been observed particularly after treatment of actively dividing gonial cells, confirming the results obtained with the same batch of the drug in a parallel collaborative investigation with Aspergillus nidulans. Thus: a) chloral hydrate has been shown to be effective in inducing nondisjunction in a mammalian system; b) a prevalent action on the mitotic spindle has been confirmed and quantified; and c) the usefulness of parallel investigations with different methods is stressed, particularly to collect information about the mechanisms of induction of nondisjunction events.

Animals↗
PubMed1984

Early deaths in acute lymphoblastic leukemia (ALL): results of the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP).

In this retrospective multicentric study, we report on early deaths (ie, those that occurred during the first month of treatment) in a total of 943 newly diagnosed ALL pediatric patients registered from 1976 to 1981 at 21 centers of the AIL- AIEOP . Objectives of this study were as follows: (1) to verify the incidence and the cause of early death in a wide population of children with ALL and (2) to elucidate factors associated with early death and therefore to identify "high-risk" groups of patients. Out of the 943 ALL patients, 39 (4.1%) early deaths were registered. Main causes were infection, 20 patients (51.3%); hemorrhage, 11 patients (28.3%); uric acid nephropathy, 2 patients (5.1%); cardiac failure, 3 patients (7.6%); syndrome of inappropriate antidiuretic hormone secretion, 1 patient. Two patients died during the first week of unknown cause. Thirteen factors measured at diagnosis and possibly influencing the early death rate were analyzed. Using the chi-square test, only three of these factors (age, mediastinum status, surface markers) appear to have any significant influence on the early death rate. We also tried to determine how therapy influences this process by analyzing variations in the early death rate, other factors being equal. Significant differences in the early death rates were encountered in AIEOP protocols using different induction regimens.

Adolescent↗
PubMed1984

Radiation response of Chinese hamster cells after elevation of intracellular glutathione levels.

Cellular glutathione (GSH) levels were modulated by either inhibition of GSH synthesis by buthionine sulfoximine (BSO) or elevation of GSH by treatment with 2-oxo-thiazolidine-4-carboxylate (OTZ), cobaltous chloride, or cysteamine. Using these agents, X ray survival in air was assessed as a function of cellular GSH levels. Depletion of GSH by BSO to less than 5% of control values resulted in slight sensitization of the aerated curve. However, elevation of GSH by as much as 200 to 300% of controls provided no radioprotection in air. These data are discussed in the context of the role of GSH and GSH peroxidase in the detoxification of peroxides produced by X rays.

Aerobiosis↗
PubMed1984

The use of halogenated thymidine analogs as clinical radiosensitizers: rationale, current status, and future prospects: non-hypoxic cell sensitizers.

The halogenated pyrimidine analogs, bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR) have been recognized as potential clinical radiosensitizers for over two decades. In vivo and in vitro experimental studies document that radiosensitization is directly dependent on the amount of thymidine replacement in DNA by these analogs. Early clinical studies in Japan using selective intra-arterial infusions of BUdR and conventional fractionated radiation suggested improved survival in patients with primary brain tumors, although there were significant catheter-related complications. Based on recent in vivo and clinical pharmacology studies on continuous intravenous infusions of these drugs, clinical trials are underway evaluating the potential of radiosensitization in high grade gliomas and other poorly radioresponsive tumors using the technically safer intravenous route of administration. In this paper, we review the basic strategy for the use of these analogs, the ongoing clinical trials and the potential areas for future experimental and clinical studies.

Animals↗
PubMed1984

131-iodine conjugated antibody cell kill enhanced by bromodeoxyuridine.

131I-conjugated monoclonal and polyclonal antibodies are being administered in vivo to kill human tumor cells. Although these conjugates deliver relatively large doses of radiation to tumors (10 to 50 Gy), the rate of dose delivery is low (0.05 to 0.2 Gy/hour). Radiation delivered at low dose rates kills fewer cells that exhibit large shoulders on radiation survival curves than radiation delivered at high dose rates. To determine whether the cell kill produced by low dose rate radiation is enhanced by a radiation sensitizer (bromodeoxyuridine, BUdR) we studied the cell kill produced by an 131I-conjugated polyclonal antibody against Chinese hamster V79 cells. V79 cells were labeled with 131I-conjugated antibody (10-20 microCi/micrograms) and unconjugated antibody, and frozen for up to 30 days in liquid nitrogen. The surviving fraction of cells was measured at intervals of 5 to 10 days. Cells not containing BUdR were also studied. The 131I-conjugated antibody produced up to 40% cell kill and BUdR increased the fraction of cells killed to 75%. Our studies demonstrate that cells frozen at -196 degrees C are useful for the investigation of the cell kill produced by isotopes that deliver radiation at low dose rates and that the cell kill caused by 131I-conjugated antibodies can be enhanced by BUdR.

Animals↗
PubMed1984

Identification of bromodeoxyuridine in malignant and normal cells following therapy: relationship to complications.

During a clinical Phase I study of bromodeoxyuridine (BUdR) as a radiation sensitizer we identified the normal and malignant cells that incorporated the BUdR. BUdR was infused for up to 14 days and the in vivo incorporation of BUdR into DNA was assessed using an immunohistochemical technique and a monoclonal antibody directed against BUdR. BUdR was identified in 50% of breast cancer cells and 10% of cells in a malignant melanoma. BUdR was also found in the basal layer of the normal epidermis and in 50% of cells in the marrow. The incorporation of BUdR into cells in the epidermis and marrow may produce the phototoxicity and myelosuppression observed in patients treated with BUdR. Sequential biopsies from a breast cancer taken prior to and following radiotherapy suggested that cells that incorporated BUdR may have been selectively killed by the radiation. The immunohistochemical technique used to identify BUdR appeared to be useful for studies of in vivo and in vitro cell proliferation.

Bone Marrow↗
PubMed1984

Differing sensitivity to fluorescent light in Chinese hamster cells containing equally incorporated quantities of BUdR versus IUdR.

Chinese hamster V79 cells that had incorporated approximately equal levels of either BUdR or IUdR into their DNA were found to be equal sensitizers to X rays. However, BUdR-substituted cells were much more sensitive to fluorescent light than IUdR-substituted cells, both on a cell survival basis and by the initial number of single strand DNA breaks induced. Since a major toxicity to the use of BUdR clinically has been light-induced skin rash, these data indicate that the use of IUdR clinically might cause less untoward toxicity but yet provide the same radiosensitization as BUdR.

Animals↗
PubMed1984

A Phase I study of intermittent intravenous bromodeoxyuridine (BUdR) with conventional fractionated irradiation.

A Phase I trial of intravenous bromodeoxyuridine (BUdR) and conventional fractionated radiation therapy was performed in 14 patients with glioblastoma multiforme and 7 patients with other poorly radioresponsive tumors. The BUdR was given as a constant intravenous infusion for 12 hr/day for up to 14 days. Thirteen patients received a second 14 day infusion following a 10 to 14 day interruption for bone marrow recovery. Local toxicity (within the radiation field) was minor, with 7 of the 21 patients requiring a brief treatment break for moist skin desquamation. There was no significant CNS toxicity noted clinically nor by autopsy examination. Additionally, no significant enhancement of radiation injury was noted to bowel or liver. However, one patient treated for multiple pulmonary metastases experienced a clinical and radiographic pattern consistent with radiation pneumonitis. Dose-dependent systemic toxicity occurred in bone marrow and skin. Moderate myelosuppression, especially thrombocytopenia, was found following a 14 day cycle of BUdR at and above 650 mg/m2/12 hr infusion. Approximately one-third of patients developed a maculo-papular erythematous rash to the scalp, neck and upper chest. In two patients, the rash became generalized with evidence of epidermolysis on skin biopsy. Pharmacology studies revealed steady-state arterial plasma levels of 2 X 10(-6) M/1 during the 12 hr infusion of 650 to 700 mg/m2. Radiosensitization was measured by a change in the D0 of radiation survival curves of human bone marrow CFUc prior to and following the 14 day infusion in 4 patients. A trend of increasing radiosensitization was noted in most patients as the infusion rate of BUdR was increased from 500 to 870 mg/m2/12 hr. We conclude that the maximum tolerable dose of BUdR is 650 to 700 mg/m2/12 hrs when given as a 2 week intermittent intravenous infusion. Local toxicity is acceptable. The major systemic toxicities are myelosuppression and a maculopapular skin rash.

Adult↗
PubMed1984

Alteration of bleomycin cytotoxicity by glutathione depletion or elevation.

In part, some of the cytotoxicity of bleomycin may be lessened or enhanced by modulation of glutathione (GSH) concentrations. Enhancement of bleomycin cytotoxicity was observed when GSH levels were low and protection was observed when GSH levels were elevated. Since H2O2 is one of the reactive species produced by bleomycin catalyzed oxygen activation, we studied the effects of H2O2 exposure after GSH depletion. H2O2, like bleomycin, shows enhanced cytotoxicity in GSH depleted cells. It has been proposed that bleomycin cytotoxicity requires reducing equivalents from non-protein bound thiols (such as GSH) to activate the bleomycin-metal complex, which in turn reacts with oxygen to generate free radicals and peroxides. Our data suggest that either GSH is not required to cycle reducing equivalents to the oxidized bleomycin-metal complex, or the low levels of depleted GSH attained (less than 5% of control) were still sufficient to effect reduction. Further, our data shows that GSH in fact provides a means of protection and detoxification from the cytotoxic effects of bleomycin. Our data suggest that caution should be exercised clinically when one uses drugs that modulate GSH because there may be either enhancement of normal tissue toxicity or decreases in tumor targeted cytotoxicity resulting from bleomycin treatment.

Animals↗