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Biomedical subjects

M Bianchi

Publications and source records attributed to M Bianchi.

At least 289 records · Page 16Linked to original sources
PubMed1986

Recombinant tumor necrosis factor depresses cytochrome P450-dependent microsomal drug metabolism in mice.

The effect of recombinant tumor necrosis factor on liver cytochrome P450 and related drug metabolism enzymes was investigated. Treatment of mice with tumor necrosis factor caused a marked depression of cytochrome P450 and some drug metabolizing enzymes (ethoxycoumarin deethylase and arylhydrocarbon hydroxylase) in the liver and many other organs. This effect was maximal 24-48 h after treatment and was dependent on the dose of tumor necrosis factor administered. Depression of liver drug metabolizing enzymes was also observed in the endotoxin-resistant C3H/HeJ strain of mice, thus ruling out that this effect may be due to minor endotoxin contamination of recombinant tumor necrosis factor. These data indicate that depression of liver drug metabolism might be an important side effect of tumor necrosis factor, and suggest a role for this macrophage product as an endogenous regulator of liver metabolism.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

Role of reactive oxygen intermediates in the hepatotoxicity of endotoxin.

Administration of endotoxin (2.5 micrograms/mouse, iv) to Corynebacterium parvum-pretreated (14 days earlier, 1 mg/mouse, i.v.) mice caused a rapid (90 min) decrease in liver cytochrome P450-dependent drug metabolism and an elevation of serum transaminase. The time course of the priming effect of C. parvum suggested that macrophages might be responsible for this sensitization to endotoxin. The antioxidant N-acetylcysteine (500 mg/kg) effectively protected against this depression of liver drug metabolism, thus supporting the hypothesis that liver macrophage-generated free radicals might mediate this hepatotoxic effect of endotoxin.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

Induction of xanthine oxidase and heme oxygenase and depression of liver drug metabolism by interferon: a study with different recombinant interferons.

Induction of xanthine oxidase in mouse liver by interferon (IFN) was studied with three different recombinant human leukocyte IFN molecules: IFLrA, IFLrD and the hybrid IFLrA/D(Bgl II). The ability of different IFN species to induce xanthine oxidase correlated with their ability to depress liver cytochrome P-450-dependent drug metabolism, supporting the hypothesis that reactive oxygen metabolites generated by xanthine oxidase might be responsible for this impairment of liver function by IFN. The antioxidant N-acetylcysteine protected in vivo against the depression of liver drug metabolism by IFLrA/D. IFLrA/D was also found to induce liver microsomal heme oxygenase, an effect that was probably secondary to the observed depression of cytochrome P-450.

Animals↗
PubMed1986

Dissociation between induction of ornithine decarboxylase and oxidative burst by phorbol esters in a macrophage cell line.

In order to investigate the correlation between stimulation of superoxide generation and induction of ornithine decarboxylase (ODC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) we have used the macrophage cell line J774.16 and a clone derived from this line that, by contrast with the parental line, is unable to generate superoxides in response to TPA. No difference was observed between the normal and the defective cells, with respect to ODC induction by TPA over a wide range of TPA concentrations (0.2-5.0 micrograms/ml). Similar results were obtained comparing resident and caseinate-elicited mouse peritoneal macrophages. Although resident macrophages did not generate superoxides in response to TPA, they did not differ from superoxide-generating, caseinate-elicited macrophages with respect to ODC induction. These data suggest a dissociation between the stimulation of the oxidative burst by TPA and a growth factor-like effect such as ODC induction.

Animals↗
PubMed1986

Role of interleukin-1 in the depression of liver drug metabolism by endotoxin.

Endotoxin-resistant C3H/HeJ mice were used to test the hypothesis that a macrophage product, possibly interleukin-1, might mediate the depression of liver cytochrome P-450-dependent drug metabolism in endotoxin-treated mice. Depression of liver drug metabolism by endotoxin was observed in normal mice (C3H/HeN) but not in C3H/HeJ mice. Serum transfer experiments demonstrated that a serum factor was responsible for the depression of liver drug metabolism. Experiments of passive transfer of peritoneal macrophages showed that this endotoxin-induced factor might be a macrophage product. In vitro experiments showed that endotoxin-stimulated monocytes produced a factor that depressed cytochrome P-450-dependent metabolism in cultured hepatocytes. Homogeneous human monocyte and recombinant interleukin-1 also depressed liver drug metabolism both in vivo and in vitro, suggesting that this macrophage product might be involved in the regulation of liver function by the immune system.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

Different sensitivity of two Walker 256 carcinoma lines to cyclophosphamide: correlation with drug distribution, biotransformation and macromolecule binding.

Two closely related lines of the same Walker 256 carcinoma in Crl-CD/COBS rats, described as behaving differently as regards tumor growth and host reaction, show different chemotherapeutic sensitivity to cyclophosphamide (CPA). Line B, which induces early cachexia with marked anorexia, is only moderately sensitive to CPA, while line A, which causes mild anorexia and only terminal cachexia, shows marked responsiveness to CPA, cure being attained in 75% of animals treated with a single dose of 120 mg/kg and in 90-100% of those given 20 mg/kg every other day. Comparative studies in both tumor lines on the distribution of CPA in vivo and on its metabolism by the liver perfusion technique showed no appreciable differences between the two lines in the pharmacokinetics of the compound, but indicate a much greater metabolizing capacity of CPA in the Walker 256/A animals. In vitro metabolic and covalent binding studies confirm that the liver of the Walker 256/A group metabolizes and covalently binds twice as much CPA as the liver of the Walker 256/B group. Conversely to Walker B, microsomal preparations of the Walker tumor line A are able to metabolize CPA to intermediates which irreversibly bind to tissue macromolecules, suggesting an in situ activation of the compound in the sensitive Walker tumor.

Animals↗
PubMed1986

[Compounds with anti-gastric secretion and antiulcer activity. V. Derivatives of 3,3,4a,6,7,11b-hexahydro-2H,5H-benzo [1,4]cyclohep[1,2-b][1,4]-oxazine and related products].

A series of hexahydrobenzo[3,4]cyclohept[1,2-b][1,4]oxazines, with different substituents at the benzene and oxazine rings and nitrogen atom, was synthetized. The diastereomers and enantiomers of the unsubstituted compound and the related derivatives hexahydrobenzo[5,6] and exahydrobenzo[6,7]cyclohept[1,2-b][1,4]oxazine, hexahydro[1]benzoxepine and hexahydro[1]benzothiepin[5,4-b][1,4]oxazine, octahydrobenzo[3,4]cyclohept[1,2-b][1,4]diazine were also prepared. Some of these compounds inhibited at low doses gastric secretion in pylorus-ligated rats and antagonized ulcers in pylorus-ligated rats plus acetylsalicylic acid and in cold+restraint-stressed rats. When the most active compounds were tested on cats with Heidenhain pouch, they induced unwanted side effects that ruled out further development of these chemical series.

Animals↗
PubMed1986

The relationship between lipofuscin and neuromelanin in some sites of the nervous system of the horse.

Histochemical and cytochemical features of neuronal pigment in the spinal cord, and in the sympathetic and spinal ganglia of the adult horse have been studied. Light and electron microscopical observations revealed that lipofuscin pigment is present in the spinal ganglia and in the spinal cord, whereas in the sympathetic ganglia both lipofuscin and neuromelanin are present. The ultrastructural studies showed that lipofuscin granules exhibited a triphasic organization consisting of a matrix, a system of lamellae and one or more lipid vacuoles. Neuromelanin granules have structural features in common with lipofuscin-like granules, except the former types store a highly electron dense material on their matrix. The electron dense material has been identified as melanin by a modification of the Lillie ferrous sulfate reaction applied at the ultrastructural level. From the ultrastructural appearance and cytochemistry of the neuronal pigments in horse it is concluded that neuromelanin should be considered as melanized lipofuscin. The possibility that the different ratio of lipofuscin to melanin within the same granule is responsible for the peculiar reaction of certain neuromelanin granules to lipophilic dyes, the PAS reaction, a histochemical assay for melanin and exposure to ultraviolet light, is discussed.

Animals↗
PubMed1985

Platelet derived growth factor induces ornithine decarboxylase activity in NIH 3T3 cells.

Incubation with highly purified human Platelet Derived Growth Factor induced ornithine decarboxylase activity in quiescent NIH 3T3 cells concomitantly with mitogenic stimulation. Pretreatment of cells with a specific ornithine decarboxylase inhibitor, DL-alpha-difluoromethyl-ornithine significantly inhibited the effect of the mitogen on DNA synthesis. These experiments suggest that the mitogenic activity of Platelet Derived Growth Factor, similarly to that of other serum growth factors or tumor promoters, is mediated through rise in polyamine levels.

Animals↗
PubMed1985

Initiation, elongation and pausing of in vitro DNA synthesis catalyzed by immunopurified yeast DNA primase: DNA polymerase complex.

Yeast DNA primase and DNA polymerase I can be purified by immunoaffinity chromatography as a multipeptide complex which can then be resolved into its functional components and further reassembled in vitro. Isolated DNA primase synthesizes oligonucleotides of a preferred length of 9-10 nucleotides and multiples thereof on a poly(dT) template. In vitro reconstitution of the DNA primase:DNA polymerase complex allows the synthesis of long DNA chains covalently linked to RNA initiators shorter than those synthesized by DNA primase alone. The SS (single-stranded) circular DNA of phage M13mp9 can also be replicated by the DNA primase:DNA polymerase complex. Priming by DNA primase occurs at multiple sites and the initiators are utilized by the DNA polymerase moiety of the complex, so that almost all the SS template is converted into duplex form. The rate of DNA synthesis catalyzed by isolated yeast DNA polymerase I on the M13mp9 template is not constant and is characterized by distinct pausing sites, which partly correlate with secondary structures on the template DNA. Thus, replication of M13mp9 SS DNA with the native primase:polymerase complex gives rise to a series of DNA chains with significantly uniform termini specified by the primase start sites and the polymerase stop sites.

Chromatography, Affinity↗
PubMed1985

E. coli recA protein possesses a strand separating activity on short duplex DNAs.

RecA protein was found to catalyze the dissociation of the strands of a DNA substrate consisting of a 20-nucleotide primer annealed to circular single-stranded M13mp DNA. The strand separation reaction requires ATP hydrolysis and the presence of single-stranded DNA flanking the duplex DNA region to be unwound. RecA-catalyzed strand separation is effective only for very short duplexes, not exceeding 30 bp, and is not stimulated by single-stranded DNA-binding protein. These results are consistent with the ability of recA protein to disrupt regions of secondary structure in single-stranded DNA and to incorporate large non-homologies into heteroduplex DNA.

DNA↗
PubMed1985

Identification of the yeast DNA polymerase I gene with antibody probes.

Partially overlapping fragments of the gene encoding yeast DNA polymerase I have been cloned by immunological screening of a yeast genomic library constructed in the phage lambda expression vector lambda gt11. The three gene fragments we analyzed in detail encode part of a yeast protein that has been identified as yeast DNA polymerase I, because it shares with this enzyme a number of antigenic determinants. In fact, the yeast protein fragments expressed by the recombinant phages react with both polyclonal and monoclonal antibodies raised against different, highly purified preparations of DNA polymerase I. Moreover, they can be used to affinity purify antibodies specifically reacting with active DNA polymerase I polypeptides and they compete with the yeast enzyme for binding to antibodies that inhibit catalytic activity. The gene is located on chromosome XIV in the yeast genome, and it is transcribed as a 5.2 kb mRNA.

Antibodies, Monoclonal↗
PubMed1985

Diagnosis of acute maxillofacial infections: the role of computerized tomography.

Most acute maxillofacial infections are diagnosed by conventional dental and maxillofacial radiographic techniques. Computed tomography has greatly improved our ability to evaluate infections of the maxillofacial region that originate or extend into the contiguous soft tissues and paranasal sinuses. Four cases in which computed tomography facilitated diagnosis and treatment of advanced infections of the maxillofacial region are presented. In one case an underlying neoplasm was identified.

Adult↗
PubMed1985

Kinetics of monosodium glutamate in human volunteers under different experimental conditions.

The kinetics of glutamic acid (GA) in plasma was studied in human volunteers after administration of monosodium glutamate (MSG) at different doses--43 mg/kg (3 g/70 kg) and 64 mg/kg (4.5 g/70 kg)--and in bouillon solutions of different concentrations (1.5-3.5%). MSG was administered to the subjects either during fasting or immediately after a standard meal. In the fasted subjects MSG administration caused a dose-dependent increase in plasma GA levels. In contrast, ingestion of MSG with a meal did not result in any significant increases in plasma GA levels in comparison with the wide variations observed in plasma GA after ingestion of a meal without added MSG.

Adult↗
PubMed1985

Strain differences in the radiosensitivity of mouse spermatogonia.

The radiosensitivity of spermatogonia was found to be greater by up to a factor of 2 in C3H mice than in B6D2F1 mice, whether assessed for the highly sensitive spermatogonia (types A2 to In) or the much more resistant clonogenic spermatogonia which repopulate tubules. The latter were similarly resistant in the B6D2F1 hybrid and in the DBA2 parent, but were much more sensitive in the C57BL parent strain. A difference in sensitivity by up to a factor of 2 results in a variation by a factor of 10 or more in the level of survival of clonogenic cells after high doses. This variation is also observed when comparing data in the literature from different authors using various strains of mice. Using the radiosensitizer misonidazole, it was shown that hypoxia did not play a major role in the lesser sensitivity demonstrated in B6D2F1 mice. The variation in sensitivity is similar to the range reported in the literature for reciprocal translocations.

Animals↗
PubMed1985

Role of reactive oxygen intermediates in the interferon-mediated depression of hepatic drug metabolism and protective effect of N-acetylcysteine in mice.

Interferon (IFN) and IFN inducers are known to depress hepatic microsomal cytochrome P-450 levels, and the liver toxicity of IFN was reported to be lethal in newborn mice. We have observed that administration to mice of IFN and IFN inducers caused a marked increase in liver xanthine oxidase activity. Because this enzyme is well known to produce reactive oxygen intermediates and cytochrome P-450 was reported to be sensitive to the oxidative damage, we have tested the hypothesis that a free radical mechanism could mediate the depression of cytochrome P-450 levels by IFN. Administration to mice of the IFN inducer polyinosinic-polycytidylic acid (2 mg/kg i.p.) caused a 29 to 52% decrease in liver cytochrome P-450. Concomitant p.o. administration of the free radical scavenger, N-acetylcysteine (as a 2.5% solution in drinking water), or the xanthine oxidase inhibitor, allopurinol (100 mg/kg), protected against the IFN-mediated depression of P-450 kg), protected against the IFN-mediated depression of P-450 levels. The results suggest that an increased endogenous generation of free radicals, possibly due to the induction of xanthine oxidase, is implicated in the IFN-mediated depression of liver drug metabolism. The relevance of these data also extends to cases in which this side effect is observed in pathological situations (e.g., viral diseases and administration of vaccines) associated with an induction of IFN.

Acetylcysteine↗