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Biomedical subjects

C Rossi

Publications and source records attributed to C Rossi.

At least 253 records · Page 14Linked to original sources

Haematological complications in polycythaemia vera and thrombocythaemia patients treated with radiophosphorus (32P).

We have evaluated 230 patients with myeloproliferative disorders treated in the last 15 years with 32P. None of the patients affected by essential thrombocythaemia developed haematological complications. In the larger group of polycythaemia patients (214 subjects) only 38 patients (17 males and 21 females) developed complications. 60.5% of these subjects had a minor complications: 1.8% showed a thrombocytopenia lower than 100.10e9/lt, 2.3% anaemia with Hb lower than 10 g%, 2.6% leukopenia lower than 40.10e9/lt and 2.3% a pancytopenia. All these complications were transient and eventually treated with limited blood transfusions. We could not identify a correlation between the dose used and the development of such complications. We noted only that the occurrence of anaemia, given a similar dose, was more frequent in females. Only 7% of all patients presented a major complication after 32P administration. In this case too, there was no correlation with the dose administered. Myelofibrosis and chronic myeloid leukaemia resulted to be the more frequent complication (9 out of 15) but we could not clarify if they represented a natural evolution of polycythaemia vera or were due to the treatment with 32P. Acute leukaemia developed only in 5 patients and again we could not recognized a correlation with the dose administered. Moreover, the time from the diagnosis of polycythaemia vera the onset of acute leukaemia ranged widely. 32P has a definite effect on the prevention of thrombotic and haemorrhagic complications in polycythaemia patients since it prolongs their life but it also increases the incidence of acute leukaemia.

Anemia↗

Isolation and characterization of carbon catabolite repression mutants in Saccharomyces cerevisiae.

Two carbon catabolite repression mutants of S. cerevisiae were isolated and characterized. In spite of the selection procedure (red colonies after tetrazolium overlay at high glucose concentration) the mutants exhibited a respiration which was as repressed as that of the parental strain or even more repressed. When grown at high glucose concentration the mutants display hyper-repression of cytochrome aa3 and of certain mitochondrial enzymes (L- and D-lactate dehydrogenases) but not of others (malate dehydrogenase, succinate dehydrogenase), indicating the existence of separate control sites for the different genes involved in the mitochondrial biogenesis. The data obtained pointed out that the same mutation affects both repression and derepression. In addition, the mutation(s) give rise to the complete derepression of the cytoplasmic enzyme NAD-glutamate dehydrogenase at 10% glucose whereas the enzyme is normally repressed at 3% glucose. The results of the genetic analysis indicate the mitochondrial nature of the mutation(s).

Carbon↗

Characterization of a novel mouse reticular cell sarcoma M5076 subline resistant to cisplatin.

A novel murine tumor resistant to cis-diamminedichloroplatinum (cisplatin, DDP) was obtained (M5/DDP) after 22 passages in which mice bearing the ovarian reticular cell sarcoma M5076 (M5) were treated with DDP. Although DDP conserved some inhibitory activity on growth of M5/DDP, it was much less effective than on M5. Treatment with DDP did not prolong the survival time of mice with M5/DDP, whereas it markedly prolonged survival of M5-bearing mice. M5 and M5/DDP tumors shared many biological and biochemical features. They were similar histologically, they metastasized reproducibly to the liver and were poorly immunogenic. Their growth rates were comparable; their DNA index, percentage of cells in S phase and intra-cellular glutathione content were also similar. In both tumors, DDP caused an accumulation of cells in S late-G2-M within 24 hr after drug treatment. However, this was efficiently reversed in M5/DDP, whereas it worsened and persisted longer in M5. Cross-resistance was observed between DDP and its analogues carboplatin and iproplatin, but tetraplatin retained marginal activity on M5/DDP tumor. Several alkylating agents tested [L-phenyalanine mustard (L-PAM); cyclophosphamide (CTX); chlorambucil (CLB); 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and dacarbazine (DTIC)] were not totally cross-resistant to DDP, but showed greater activity on M5 than on M5/DDP. Other non-alkylating anti-neoplastic drugs showed a similar degree of activity on M5 and M5/DDP. 5-Aza-2'-deoxycytidine (Aza-d-Cyd) was very effective on both tumors, etoposide (VP-16) and cytosine arabinoside (Ara-C) had no activity and Adriamycin (ADR) was weakly effective.

Animals↗

Numerical simulation of a stochastic model for cancerous cells submitted to chemotherapy.

A stochastic model is proposed to study the problem of inherent resistance by cell populations when chemotherapeutic agents are used to control tumor growth. Stochastic differential equations are introduced and numerically integrated to simulate expected response to the chemotherapeutic strategies as a function of different parameters. Satisfactory demonstration runs of the model indicate that it could represent a useful tool in verifying the results of experimental and clinical chemotherapy courses and planning treatment strategies. Some types of behaviour are illustrated graphically.

Drug Resistance↗

A stochastic model of the acquisition of drug resistance during antineoplastic chemotherapy.

A stochastic model is proposed to simulate the phenomenon of acquisition of genetic resistance by a tumor cell population treated with antineoplastic cytotoxic agents. In the model, stochastic differential equations are numerically integrated to simulate the expected response after treatment with two different agents. The model takes into account the initial number of cells, the sequence of the agents, the time intervals between administrations, the birth and death rates of the untreated cells, the probabilities of mutations to resistance, and the induced cell-killing kinetics. Satisfactory demonstration runs of the model indicate that it could represent a useful tool in verifying the results of experimental and clinical chemotherapy courses and planning treatment strategies.

Antineoplastic Agents↗

Primary lung melanoma.

A rare case of primary malignant melanoma of the lung in a 30 year-old female is reported. A chest x-ray and C.T. scan revealed a mass 3 cm in diameter. The patient underwent left lower lobectomy for cure.

Adult↗

[Total proteins levels and embryonic development of eggs of sea urchins (Lytechinus variegatus) treated with YbCl3].

Total proteins levels and the embryonic development of sea urchin (Lytechinus variegatus) eggs treated with 25 micrograms/ml of YbCl3 in sea water for one hour were studied. After the treatment, eggs were let to develop for 24 hours when the total proteins levels were determined and morphological changes as well as the synchronism of the embryonic development have been checked.

Animals↗

Potentiation of adoptive immunotherapy by cis-diamminedichloroplatinum(II), but not by doxorubicin, on a disseminated mouse lymphoma and its association with reduction of tumor burden.

The therapeutic effect of a combination therapy employing syngeneic anti-tumor immune T lymphocytes and either doxorubicin (DX) or cis-diamminedichloroplatinum II (DDP) was tested on BALB/c mice bearing a disseminated, weakly immunogenic lymphoma (YC8) which metastasizes mainly to the liver. Therapy with specific tumor-immune lymphocytes alone cure 80-100% mice bearing 3-day established tumors. The same effector cells, however, were less effective in mice at a more advanced stage of the disease (day 5) and ineffective when treatment was further delayed (day 7). Chemotherapeutic treatment alone with DX or DDP given i.p. at the maximal tolerated doses was less effective than immune lymphocytes on 3-day tumors since cures were very seldom observed, but both drugs prolonged survival time even when administered on day 7. While DX did not enhance the antitumor effect of immune lymphocytes on 5-day tumors, the association of DDP with immunotherapy by giving the 2 modalities sequentially according to the two sequences (i.e., chemotherapy before immunotherapy and vice versa) with a 2-day interval, was significantly more effective than each treatment alone. Like mice cured by immunotherapy alone, most of the animals cured by chemo-immunotherapy developed a systemic transplantation immunity to the tumor as revealed by the specific rejection of a second lethal tumor challenge 90 days after the first tumor inoculum. The higher activity of DDP compared with DX in potentiating the effect of immunotherapy was shown to be associated with a greater reduction of tumor burden in the liver, whereas the 2 drugs gave a similar reduction of tumor burden in other organs, as determined from bioassay of tumor-bearing organs of chemotherapy-treated mice. These results indicate that combination of chemotherapy with immunotherapy may improve the effects of each treatment alone, and that the synergistic effect is associated with the reduction of the tumor load in the main organ (liver) of tumor dissemination.

Animals↗

Dose-dependent pharmacokinetics of flavone acetic acid in mice.

The pharmacokinetics of the novel anticancer agent, flavone acetic acid (FAA) were investigated in Balb-c mice treated with i.v. doses of 100 mg/kg or 300 mg/kg, using an HPLC assay. The kinetics of disappearance from plasma was monoexponential and dose-dependent. After 100 mg/kg, the plasma peak level was 250 +/- 11 micrograms/ml, t1/2 was 0.5 h, and AUC was 309 micrograms/ml per h. After 300 mg/kg, the plasma peak level was 710 +/- 57 micrograms/ml, t1/2 was 2.1 h, and the area under the curve (AUC) 1771 micrograms/ml h. Mouse plasma protein binding of FAA was about 70%. As is the case with plasma, in all tissues analyzed, the FAA-AUC values were disproportinately greater after 300 mg/kg than after 100 mg/kg. The highest drug concentrations were found in the liver and small intestine; concentrations were intermediate in lung, heart, and spleen, and lowest in brain. Less than 5% of the FAA dose was eliminated as unchanged drug in the stool. Total excretion of FAA as unchanged drug in the urine collected up to 96 h after drug treatment corresponded to 75% and 60% of the i.v. doses of 100 and 300 mg/kg, respectively. A minor fraction of FAA dose, corresponding to 1% and 6% of the two doses, was eliminated in the urine as a FAA glucuronide or sulfate.

Animals↗

CA 19-9 determination in gastric juice: role in identifying gastric cancer and high risk patients.

Gastric juice CA 19-9 levels were determined in 23 patients affected by gastric cancer, in 57 patients affected by chronic atrophic gastritis of different severities and in 55 'healthy' controls, undergoing endoscopy for upper gastrointestinal tract symptoms. Increased CA 19-9 levels were documented in chronic atrophic gastritis patients as well as in gastric cancer patients, the difference with respect to controls being statistically significant. However, there was considerable overlap between different groups. In particular, gastric cancer patients had CA 19-9 levels similar to those detected in moderate and severe chronic atrophic gastritis. CA 19-9 correlated with gastric juice pH and CEA concentration. Its values were not influenced by the patients' age or sex. In our opinion CA 19-9 gastric juice determination, although not useful in singling out patients harboring gastric neoplasia, may be used in identifying patients 'at risk' for gastric cancer and who might then be referred for more accurate investigations.

Adult↗

Rickettsiae of the spotted fever group associated with the host-parasite system Oryctolagus cuniculi/Rhipicephalus pusillus.

Wild rabbits--Oryctolagus cuniculi--living in large numbers in a protected zone of Tuscany, the park of Migliarino--San Rossore--Massaciuccoli, showed to be carriers of the hard tick Rhipicephalus pusillus, previously observed in North Africa and Sicily. Antibodies to Rickettsia conorii and R. slovaca were detected in 78.9 per cent of the wild rabbits captured in that area. Seroconversion towards R. conorii was also observed in guinea pigs inoculated with homogenates of R. pusillus parasitizing the wild rabbits. These results identify an ecological niche of rickettsiae of the Spotted fever group in the host-parasite system O. cuniculi/R. pusillus. Attempts to isolate rickettsiae from the ticks and the wild rabbits were unsuccessful both in the egg yolk sac and in the guinea pig. This failure probably shows the low pathogenicity of the rickettsiae parasitizing the biosystem O. cuniculi/R. pusillus.

Animals↗

Evidence of human infection with a rat-associated Hantavirus in Baltimore, Maryland.

Human sera obtained from two sources in Baltimore were tested for antibodies against a Hantavirus by a variety of techniques. Four persons out of 1,788 had hantaviral antibody as demonstrated by immunofluorescent assay, enzyme-linked immunosorbent assay, and neutralizing assay. Neutralizing antibody titrations against three test viruses indicated that infections were caused by a rat-associated virus. Medical histories of two subjects indicated life-long residence in Baltimore and an absence of foreign travel, implicating a local source of infection.

Adolescent↗

Evaluation of the mutagenic activity of leucinostatins, a novel class of antibiotic peptides produced by Paecilomyces marquandii, in the modul Aspergillus nidulans.

Leucinostatins A, B, C, D, E, G, H, and K were thoroughly investigated for their genotoxic activity using the modul Aspergillus nidulans as the test organism. The results of assays for gene mutation (8-azaguanine resistance and methionine suppressors), gene conversion, mitotic crossing-over and mitotic aneuploidy induction suggest that these peptide antibiotics lack significant mutagenicity and that non-genotoxic mechanism(s) underlie their cytotoxic properties.

Anti-Bacterial Agents↗

[Temporal lobe epilepsy. Developmental psychiatric study of a surgically treated series].

The authors have studied psychiatrically, pre and post-operatively, a series of 31 cases operated upon for temporal lobe epilepsy. They have concluded that medically uncontrollable limbic epilepsy is associated in its physiopathological substrate to: pathological irritability, affective tenacity, impulsiveness, epileptic cognitive dysfunction and abstraction deficiencies of intellectual process. The high incidence of these events in the patients studied demonstrate the existence of a causal relationship between these abnormalities and the limbic epilepsy. Unilateral temporal lobectomies have been demonstrated to be very efficient for the control of epileptic seizures, whose frequency was remarkably reduced post-operatively. The operation resulted in a major reduction of the psychiatric manifestations of pathological irritability, impulsiveness, epileptic cognitive dysfunction and the instability of abstraction capacity produced by affective impacts. Affective tenacity was ill affected by the surgical procedure, although a favourable effect was noticed. The presence of bilateral temporal foci did not decrease the efficacy of the surgical intervention, nor its effect on the seizures or the effect of surgery on the studied psychopathological changes.

Adolescent↗

Effectiveness of a rapid immunohistologic method for tumor cell origin analysis.

A rapid immunohistologic method is described to analyze the possible cell origin of a given neoplasm during surgery by using selected examples of monoclonal and polyclonal antibodies (anti-cytokeratins, anti-vimentin, anti-leukocyte common antigen, and anti-keratin). This rapid (26-28 min) procedure, consisting of a two-step immunoperoxidase method, did not differ in terms of intensity and specificity of the immunoreaction from the control procedure for which conventional longer times of incubation and washing were used. The results demonstrate the feasibility and effectiveness of the procedure.

Antibodies, Monoclonal↗

Markedly different ATP requirements for rRNA synthesis and mtDNA light strand transcription versus mRNA synthesis in isolated human mitochondria.

In isolated mitochondria from HeLa cells, the ATP requirements for mitochondral DNA (mtDNA) transcription and RNA processing can be satisfied by either endogenous synthesis, mainly through oxidative-phosphorylation, or by exogenous supply. The pattern of RNA synthesis changes dramatically depending upon the level of ATP available. At the low intramitochondrial ATP levels produced from endogenous ADP in the presence of an oxidizable substrate and phosphate, the mRNA species are labeled to a substantial extent, whereas there is only a marginal labeling of the rRNA species and light (L) strand transcripts. By contrast, high ATP levels, either provided exogenously or produced endogenously in the presence of an oxidizable substrate, phosphate, and exogenous ADP, strongly stimulate rRNA synthesis (about 10-fold) and light (L) strand transcription (greater than 10-fold), with only a slight increase in mRNA synthesis.

Adenosine Triphosphate↗