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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 631 records · Page 35Linked to original sources
PubMed1984

The effects of glutathione depletion on thermotolerance and heat stress protein synthesis.

The effects of cellular glutathione depletion by buthionine sulfoximine on the development of thermotolerance and synthesis of heat stress protein was studied. Cellular glutathione levels were found to increase rapidly following an acute heat treatment of either 12 min at 45.5 degrees C or 1 h at 43 degrees C and remain elevated for prolonged periods. Glutathione depletion and prevention of glutathione synthesis by buthionine sulfoximine resulted in inhibition of the development of thermotolerance and a decrease in total protein as well as specific heat stress proteins. While the degree of inhibition of thermotolerance was similar for both glutathione depletion protocols, inhibition in heat stress protein synthesis was greater when glutathione was depleted to low levels prior to heating. The possible role of glutathione and the cellular redox state to thermotolerance and synthesis of heat stress protein is discussed.

Animals↗
PubMed1984

Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer.

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10(-7) mol/L and 1 X 10(-6) mol/L during infusion of 650 and 1,000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1,000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). We conclude that local and systemic toxicity of continuous infusion of BUdR at 1,000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with our previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

Bone Marrow↗
PubMed1984

Prognosis of the so-called "diffuse" cerebellar astrocytoma.

The term "diffuse cerebellar astrocytoma" was originally introduced by Russell and Rubinstein to describe that minority of cerebellar tumors microscopically similar to the cerebral hemispheric astrocytoma. The aim of this study was to verify some recent reports warning against the less favorable long term prognosis of the "diffuse" form of the cerebellar astrocytoma. We reviewed our series of cerebellar astrocytomas in children and collected 49 cases operated on before 1966 (i.e., with a follow-up ranging from a minimum of 15 years to 29 years). In addition, we reexamined all recurrent cerebellar astrocytomas observed during a 30-year period, looking for the eventual occurrence of the "diffuse" form. In the first group, 10 cases (20%) were classified as "diffuse" and 39 cases (80%) were classified as "classic". However, in 3 cases largely featuring a diffuse pattern, we also noted some areas of the classic type. These two subgroups showed no significant differences in patient sex and age, the incidence of macrocysts, the surgical technique used, the eventual x-ray therapy, and the long term functional results (P greater than 0.05). When we studied recurrent tumors that were reoperated on, we did not find any case showing histologically the "diffuse" pattern. To conclude, we cannot agree with the pessimism about the ominous long term prognosis of the diffuse cerebellar astrocytoma. In our opinion, the so-called diffuse cerebellar astrocytoma does not exist as a separate clinicopathological entity.

Adolescent↗
PubMed1984

Diagnosis of superior sagittal sinus thrombosis by computerized tomography. Report of two cases.

Superior sagittal sinus thrombosis was diagnosed on computerized tomography (CT) scanning and was subsequently confirmed by angiography in two patients. Small ventricles and filling defects occurring within the sinus (the empty triangle sign) appeared to be highly suggestive of superior sagittal sinus thrombosis, and the association was confirmed angiographically. Potential pitfalls in the CT diagnosis of local obstruction of cerebral venous outflow are described and correlated with the natural history of the disease. The need for improved awareness of the CT appearance of occlusive disease of the dural venous sinuses is stressed.

Adult↗
PubMed1984

Factors influencing the oxidation of cysteamine and other thiols: implications for hyperthermic sensitization and radiation protection.

Some of the factors influencing the oxygen uptake and peroxide formation for cysteamine (MEA) and other thiols in serum-supplemented modified McCoy's 5A, a well-known medium used to cultivate a variety of cells in vitro, have been studied. The oxidation of MEA and cysteine in modified McCoy's 5A has been compared with that in Ham's F-12, MEM, and phosphate-buffered saline. All of the growth media were supplemented with 10% calf serum and 5% fetal calf serum. The rate of oxygen uptake for all of the studied thiols was greatest in McCoy's 5A. The data indicate that this medium may contain more copper than the other preparations. MEA and cysteine were found to be more effective at 0.4 mM at producing peroxide than dithiothreitol (DTT). N-acetylcysteine was the least reactive. The ability to produce peroxide is dependent upon the temperature, the concentration of thiol, the presence of copper ions, and pH of the medium. MEA and other thiol oxidation is inhibited by the copper chelator diethyldithiocarbamate. Catalase also reduces the oxygen uptake for all thiols. This inhibition involves the recycling of peroxide to oxygen. Superoxide dismutase (SOD) was found to stimulate the oxygen uptake in the case of MEA and cysteine, but had little or no effect with DTT and glutathione. The combined presence of SOD and catalase resulted in less inhibition of oxygen uptake than that obtained by catalase alone. Alkaline pH was found to enhance the oxidation of cysteine and MEA. An important observation was the inhibition of MEA oxidation at 0 degrees C and the stimulation at 42 degrees C. The results indicate that many problems may arise when thiols are added to various media. A major consideration is concerned with the production of peroxide, superoxide, and reduced trace metal intermediates. The presence of these intermediates may result in the production of hydroxyl radical intermediates as well as the eventual oxygen depletion from the medium. Oxygen depletion may alter the results of radiation sterilization and carcinogen activation. Radical production will cause cell damage that is temperature dependent. Therefore, careful consideration must be given to changes in oxygen tension when thiols are added to cells growing in complicated growth medium to protect against either chemical or radiation damage.

Catalase↗
PubMed1984

Heterogeneity in the radiation survival curves and biochemical properties of human lung cancer cell lines.

Human lung cancers of distinct histology exhibit different responses to radiation therapy in vivo. For examination of the basis of this phenomenon, the radiation survival curves and levels of relevant enzymes were determined in 16 lung cancer cell lines derived from tumors of different histology. These included lines from 5 adenocarcinomas, 7 small cell tumors, 3 variant small cell tumors, and 1 large cell tumor. These findings were compared to those obtained with the use of a normal skin fibroblast cell line. Whether cloned in liquid culture or soft agarose, cell lines had similar radiation survival curves. These curves were consistent with the apparent in vivo radiation responsiveness of the tumors. Although considerable heterogeneity in radiation survival curves was observed among the cell lines, cells from large cell lines and small variant lines had pronounced shoulders and extrapolation numbers (n) from 5.6 to 14. In contrast, cells from small cell lines and adenocarcinoma cell lines were more "sensitive" (-n values of 1-3.3). In these cell lines, levels of DNA polymerase beta, glutathione (GSH), GSH transferase, GSH reductase (NAD(P)H), gamma-glutamyltransferase did not correlate with radiation parameters of sensitivity. DNA polymerase beta and GSH levels were, however, higher than those in a line of normal skin fibroblasts. These cell lines may be useful in identifying the basis of the variable responsiveness of human lung cancer cells to ionizing radiation.

Cell Line↗
PubMed1984

Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors.

Previously, 5-bromodeoxyuridine (BrdUrd) has been shown to be an effective radiosensitizing agent in rapidly dividing cells. As part of a Phase I/II study to evaluate BrdUrd as a radiosensitizer in gliomas, the pharmacology was studied in eight patients. BrdUrd was infused using an i.v. route as a 12-hr constant infusion each day for as long as 14 days. BrdUrd steady-state arterial levels are described for three different infusional rates: 1.6 mumol/sq m/min (350 mg/sq m/12 hr) produced a steady-state arterial level of 0.7 microM; 3.2 mumol/sq m/min (700 mg/sq m/12 hr) resulted in 2.1 microM; 5.9 mumol/sq m/min (650 mg/sq m/6 hr) showed a level of 3.9 microM. Because of myelosuppression, the highest tolerable dose for this intermittent long-term infusional therapy with BrdUrd appears to be 700 mg/sq m/12 hr. Contrary to the nonlinear pharmacokinetics of thymidine, 5-fluorouracil, and 5-fluorodeoxyuridine described previously, BrdUrd shows linear behavior in the range studied. BrdUrd still has promise as a radiosensitizer for gliomas in humans, but an alternative means of safe delivery into the carotid artery is needed. Because of an estimated 11- to 16-fold-higher local concentration, use of the intraarterial route could deliver optimum levels of BrdUrd to the tumor with minimal systemic toxicity.

Brain Neoplasms↗
PubMed1983

Unusual combination of genetic defects in a Sicilian boy: G gamma delta beta thalassemia, G gamma A gamma heterocellular HPFH, beta (0) thalassemia, and albinism.

We describe the clinical and hematological findings in a 5-year-old boy with G gamma A gamma delta beta thalassemia, a G gamma A gamma heterocellular form of HPFH, beta(0) thalassemia, and albinism. Clinically he manifested only the characteristics of beta-thalassemia trait and not the typical picture of doubly heterozygous beta thal/delta beta thal. The simultaneous presence of heterocellular HPFH improves gamma chain synthesis, thus reducing the alpha chain excess. It is also possible that gene expression can be modified by the presence of other genetic anomalies.

Albinism↗
PubMed1983

Effects of hypothalamic lesions on the content of dynorphin immunoreactivity in pituitary.

Radiofrequency lesion of medial basal hypothalamus (MBH) caused a approximately 50% depletion of immunoreactive dynorphin (ir-dyn) both in the anterior and neurointermediate lobe of the pituitary, whereas radiofrequency lesions of both supraoptic and paraventricular nuclei (SON, PVN) resulted in an approximately 30% reduction in neurointermediate lobe only. MBH cells and/or fibers contribute, therefore, to adenohypophysis pool of ir-dyn. Moreover, since the loss of ir-dyn in neurohypophysis ascertained after MBH lesion is significantly higher than that obtained with SON and PVN destruction, it may be assumed that MBH also participate to ir-dyn pool in neurohypophysis.

Animals↗
PubMed1983

Radiosensitization of hematopoietic precursor cells (CFUc) in glioblastoma patients receiving intermittent intravenous infusions of bromodeoxyuridine (BUdR).

The potential use of bromodeoxyuridine (BUdR) as a radiosensitizer given by an intermittent intravenous route is being studied in a Phase I/II trial at the National Cancer Institute. In order to assess the extent of radiosensitization, we have studied the radiation response of human bone marrow cells CFUc taken from 6 patients prior to and after a 14-day infusion of BUdR. Varying concentrations (1000-1500 mg) of BUdR were infused for 12 hours every 24 hours for up to 14 consecutive days. Cell survival was determined by colony formation of CFUc in soft agar suspension. X ray survival curves were generated over a dose range of 0-300 rad and the slopes of the survival curves (DO) before and after BUdR infusion were compared. Radiation enhancement ratios (ER) (DO pre-BUdR/DO post-BUdR) ranged from 1.0-2.2 and appeared to be BUdR dose dependent. Above 650 mg/m2, the radiation ER was greater than or equal to 1.5. Dose dependent systemic toxicity to bone marrow and skin was also observed with intermittent intravenous infusions of BUdR. From our study, it appears that an intravenous dose of less than 700 mg/m2/12 hours is well tolerated and may result in radiosensitization of CFUc in man.

Adult↗
PubMed1983

Reciprocal translocations in ageing mice and in mice with long-term low-level 239Pu contamination.

Single intravenous injections of 185 Bq monomeric 239Pu were given to male mice, and the frequency of primary spermatocytes with reciprocal translocations, determined 724 days after treatment, was not significantly different from that of age-matched untreated controls. These old animals showed significantly higher aberration frequencies than young adults. The data therefore show that for low initial activity and very long retention time the possible cytogenetic effects of incorporated nuclide does not change the age-related pattern of increase of spontaneous chromosome aberrations. Considerations of the main variables involved in the induction of cytogenetic effects of incorporated plutonium, based on literature data, indicate that the initial injected activity, the estimated total accumulated average organ dose, and the retention time interact in a complex way; as far as can be seen at present, the effects seem to be dependent mainly on the initial activity at short times after contamination, while the retention time appears to be predominant in the case of long-term observations.

Aging↗
PubMed1983

Unusual combination of genetic defects in a Sicilian family: beta-thalassaemia, haemoglobin Lepore Boston-Washington and heterocellular hereditary persistence of fetal haemoglobin.

This paper reports a Sicilian family in which beta-thalassaemia, haemoglobin Lepore Boston-Washington and heterotocellular hereditary persistence of fetal haemoglobin (HPFH) were present in various combinations. The most interesting combination was that of Hb Lepore and heterocellular HPFH, which has not been previously reported. This subject was clinically normal, with the haematological picture of Hb Lepore trait and an unusually high level of HbF due to an increased number of circulating F cells.

Adult↗
PubMed1983

The penetration of phenobarbital in generalized and focal penicillin-induced epileptic brain of the cat.

The penetration of phenobarbital (PB) into cerebral tissue was determined in cats rendered epileptic by parenteral penicillin and in cats with focal penicillin-induced epilepsy. The results were compared with those from normal controls. In both kinds of experimental models of epilepsy, PB penetration was impaired, although a gradual and progressive accumulation of the drug in the brain tissue was observed in all three groups of cats (binding occurring from time 30 min on). Similar to the events with other substances, such as carbamazepine, the prolonged epileptic activity may have contributed to the impaired penetration of PB, because of severe metabolic alterations secondary to seizures. The present data confirm previous reports indicating that epileptic seizures alter the pharmacokinetics of drugs.

Absorption↗
PubMed1983

Cystic cerebral astrocytomas in infancy and childhood: long-term results.

24 cases of cystic cerebral astrocytoma represent 11% of 217 supratentorial tumors of the pediatric age group operated. Both macro- and microscopically, such tumors resembled in most cases the well-known cerebellar astrocytoma, presenting as a large cyst with a mural nodule with the pattern of a pilocytic astrocytoma (i.e. spongioblastoma of the German school). The preferential site of incidence was the temporal lobe and the age peaks were of 7 and 16 years without sex prevalence. The surgical technique consisted in the extirpation of the mural nodule, preceded by emptying the cyst, followed by opening the contiguous ventricular wall. The extirpation was partial in one-third of the cases of whom the minority underwent radiotherapy. 1 patient died after the operation while 2 others died from tumor recurrence after 3 and 4 years, respectively, both being mixed tumors (oligoastrocytoma) that were irradiated postoperatively. The follow-up ranged from 10 to 29 years in 70% of the cases. The long-term functional results of the available 17 patients are as follows: good (perfectly well), 12 cases (70%); fair (minor troubles), 5 cases (30%). 3 of the 5 cases with a fair result all had a partial resection.

Adolescent↗
PubMed1983

Lymphocyte changes in favism: in vitro evidence of a modifying effect of bilirubin and hemoglobin on T-lymphocyte receptors.

Lymphocyte subpopulations were studied in 13 Sicilian glucose-6-phosphate dehydrogenase (G6PD)-deficient children during and after the hemolytic crisis due to fava bean ingestion. A statistically significant reduction of sheep-red-cell (SRC)-rosetting lymphocytes occurred in all patients during the hemolytic crisis, whereas B lymphocytes were not affected. In order to establish the possible relationship between serum changes occurring during hemolysis and reduction of SRC-rosetting lymphocytes, the effect in vitro of varying concentrations of bilirubin and hemoglobin on the rosette formation capacity of lymphocytes was studied. Both substances produced a statistically significant reduction of SRC-rosetting lymphocytes both in normal and deficient subjects. This effect showed a direct relationship with the concentrations of bilirubin and hemoglobin used and was more pronounced on lymphocytes from G6PD-deficient children. These data suggested that the reduction of SRC-rosetting lymphocytes observed during acute hemolysis of favism can be related to a modifying effect of bilirubin and hemoglobin.

Bilirubin↗