PubMed HealthSearch

Biomedical subjects

J Major

Publications and source records attributed to J Major.

16 recordsLinked to original sources

The effect of D-penicillamine on CCl4-induced experimental liver cirrhosis.

The effect of D-penicillamine (Pe) on liver fibrosis-cirrhosis induced by chronic CCl4 and phenobarbital (Pb) administration in Fischer 344 male rats was studied. Morphometric analysis did not reveal a decrease in the amount of connective tissue fibers after Pe-treatment. Compared to the CCl4 and Pb-treated control groups, Pe had no significant effect on the concentrations of hydroxyproline, a parameter of collagen degradation, either; however, it increased the glycosaminoglycan concentrations. Lymphocyte stimulation by Con-A in the Pe-treated groups did not differ from that of the CCl4 and Pb-treated ones. According to our studies, Pe-treatment was ineffective in rats with liver fibrosis-cirrhosis induced by CCl4 and Pb administration. It seems that Pe can be effective only in the cirrhosis types accompanied by a considerable copper accumulation due to suppression of the toxic effects of copper.

Animals

Normal controls and biological reference values in child psychiatry: defining normal.

About half of adults volunteering as normal control research subjects may be rejected because of significant psychopathology, but no parallel study has been done to date for pediatric subjects. Of 152 applicants (ages 6 to 18) for participation as paid normal controls, 44% were found ineligible and at least 31.8% of the child volunteers had probable or certain psychiatric disorders. Successive screenings, including rating scales and structured interviews, were necessary to obtain controls meeting a defined standard of psychiatric health. Careful scrutiny of child volunteers in biological psychiatric research is needed to assure meaningful comparisons.

Adolescent

[The effect of D-penicillamine on experimental liver cirrhosis induced by CCl4].

Authors examined the effect of D-penicillamin (Pw) on liver cirrhosis induced by chronic CCl4 and phenobarbital (Pb) treatment in Fischer 344 rats. Morphometric analysis of quantity of connective tissue fibres did not show decrease on the effect of Pe treatment. Quantity of hydroxiproline, which is one of the parameters of coll ahen decrease, did not change significantly on effect of drug, but only compared to CCl4 and Pb treated control. Quantity of glycosaminoglycan showed increase following Pe treatment. Lymphocyte stimulation by Con-A was different in CCl4 and Pb and Pe treated groups, respectively. According to our examinations in case of liver fibrosis cirrhosis induced by CCL4-PB treatment in rats the Pe treatment proved to be unsuccessful. It seems that Pe is effective only in forms of cirrhosis accompanied by significant copper accumulation, by decrease of toxic effects of copper.

Animals

Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells.

The mechanism of action of 5-hexyl-2-'deoxyuridine (HUdR), a compound with antitumor activity, has been investigated in the HM cell lines derived from the highly metastatic variant of Lewis lung carcinoma (3LL-HH). It was shown that this pyrimidine analog did not inhibit the biosynthesis of nucleotides but modified the biosynthesis of glycoconjugates. The incorporation of [14C]-glucosamine into cytoplasmic glycoconjugates [glycosaminoglycan (GAG), glycolipid (GL), glycoprotein (GP), neutral polysaccharide (NP)] decreased to a similar level. The [14C]-glucosamine derived radioactivity was reduced to about 60-70% of the untreated controls in the presence of 15 micrograms/ml HUdR, which caused no inhibition of cell proliferation. These results might be explained by the reduced conversion of glucosamine into uridine-5'-diphospho-hexosamine. As more reduction was observed in the glucosamine labeling of glycoconjugates in nuclei and extracellular compartment, it may be conceivable that the intracellular transport of certain glycoconjugates (GAG, GP) is also affected by HUdR. In the extracellular compartment the reduced level of GAG labeling was the most apparent change. However, at a higher concentration of HUdR (75 micrograms/ml) there was a higher radioactivity in the combined GL + GP fraction. Using [35S]-labeling, the GAG fractions also showed a decreased radioactivity but only at the concentration of 75 micrograms/ml HUdR.

Antimetabolites, Antineoplastic

Lipopolysaccharide-inducible macrophage early genes are induced in Balb/c 3T3 cells by platelet-derived growth factor.

We have previously described the isolation and characterization of a set of cDNA clones encoding lipopolysaccharide (LPS)-induced early genes in murine peritoneal macrophages. The treatment of macrophages with LPS also stimulates the expression of four early or competence genes (c-fos, c-myc, JE, and KC) described in platelet-derived growth factor-stimulated Balb/c 3T3 cells. These latter findings led to the hypothesis that long term, adaptive responses such as DNA synthesis in fibroblasts and functional activation of macrophages may share multiple mechanistic pathways. To test this possibility, we have examined the expression of four LPS-inducible macrophage genes in platelet-derived growth factor-stimulated Balb/c 3T3 fibroblasts. The results demonstrate that three of these four genes are expressed in 3T3 cells in a fashion reminiscent of other growth factor-stimulated competence genes. All three mRNAs are expressed even in the presence of cycloheximide and two of the three exhibit superinducibility. The accumulation of these specific mRNA species was dependent upon the stimulation of transcription as determined by nuclear "run-off" studies. The platelet-derived growth factor dose dependence is comparable both for stimulation of DNA synthesis and expression of the three early genes. Furthermore, expression of all three genes preceded the entry of the cells into S phase, suggesting an association with cell cycle entry. Stimulation of 3T3 cells with epidermal growth factor resulted in DNA synthesis but not early gene expression. This latter result indicates that these early gene products are not necessary for 3T3 cell mitogenesis. Nevertheless, the expression of these genes in two different cell types in association with two distinct functional responses suggests that they contribute common functions either in terms of the physiologic response in which these cells participate (e.g. inflammation) or in the regulatory mechanisms which govern such responses.

Animals

[Early experience with the use of the Halo device in the treatment of damage to the cervical spine].

Authors report on their experiences gained in 5 cases with the Halo device. The method of treatment is described. On the basis of a literary overview the field of indication, the advantages and the disadvantages of the method are described. In the assessment of the method it is stressed that according to their opinion this is the best conservative method of treatment, and the results compete with that of the operative treatment.

Bone Screws

Spectrum of operations on the cervical spine in a neurosurgical spinal centre with trauma profile.

A statistical review is given about the treatment in the Neurosurgical Department of our Institute of cervical spine injuries and non-traumatic spinal diseases during 11 years, as well as about the trends of development in spine surgery. The ratio of operative and conservative methods is described, analysing the indications and yearly numbers of different surgical procedures as compared to the data of non-traumatic spinal diseases. Altogether 786 patients were treated, 319 operations were performed on the cervical vertebral column. By the follow-up of different surgical techniques a radical change of attitude has been shown: ventral desis has got the leading role instead of dorsal spondylodesis which formerly used to be the method of choice. In addition, combined dorsal and ventral desis, lateral exposure, screw-fixation of the dens axis and the Halo-method are important techniques of the up-to-date treatment in special types of injuries.

Cervical Vertebrae

Inhibitory effect of hypophysectomy and food restriction on glomerular basement membrane thickening, proteinuria and renal enlargement in aging male Wistar rats.

Age-related thickening of the glomerular basement membrane (GBM) was studied in three groups of male Wistar rats: (a) ad libitum fed, (b) hypophysectomized and (c) food-restricted eating the same amount of food as hypophysectomized rats, but about 45% of the ad libitum fed group. Studies were begun at 50 days (2 months) and continued throughout life. Multiple regression was used to statistically assess the effects of age and treatments. In ad libitum fed male rats GBM thickness increased from 114 nm at 50 days (2 months) to 632 nm at 1,000 days (33 months). GBM thickness at 1,000 days was 296 nm in hypophysectomized rats and 392 nm in food restricted rats. Hypophysectomy had a significantly greater inhibitory action on GBM thickening than food restriction, in rats eating the same quantity of food per day. However, a major part of the effect of hypophysectomy may be due to the permanent fall in food intake (from 16.3 to 7.9 g/day) resulting from the operation. Accompanying the age-related thickening of the GBM in ad libitum fed rats were proteinuria and renal enlargement, both of which were inhibited by hypophysectomy and food restriction.

Aging

Immunoregulating peptides II. In vitro effects of TP5 analogs on E-rosette formation and cell division.

The effects of seventeen synthetic analogs of thymopentin (TP-5) have been studied in the active and azathioprine-inhibited E-rosette tests. Thymopentin was gradually shortened from the C terminus to peptides and single amino acids. Thymopoietin 32-34 (Arg-Lys-Asp-RGH-0205-TP-3) (II) and thymopoietin 32-35 (Arg-Lys-Asp-Val-RGH-0206-TP-4) (I) were the most active peptides. Dipeptide Arg-Lys produced significant stimulatory effect on azathioprine (ED75) inhibited E-receptor. Treatment of azathioprine (ED75)-inhibited E-rosette forming cells (ERFC) with arginine or especially lysine increased the number of ERFC. Some of TP-4 analogs decreased further the number of ERFC decreased by azathioprine ED30. These "suppressive" peptides as well as TP-3 caused a partial arrest of K 562 cell proliferation up to 96 hours. Results suggest that TP-5 is not the smallest active fragment of thymopoietins, since peptides (TP-3 and TP-4) exhibit similar or higher T-cell membrane activation on E-receptor. Arginine, lysine, and acidic aspartyl residue seem to be a necessary basic structure to produce a cumulative chemical signal on the activity of T-lymphocytes.

Adjuvants, Immunologic

Chemotherapy of human non-Hodgkin lymphoma (NHL) xenografts.

Three human NHL (B-cell type) were established successfully as serially transplantable xenografts in artificially immunesuppressed CBA mice. All of them preserved the phenotypic characteristics of the original tumour even after several passages. The transplanted tumours were highly sensitive to cyclophosphamide and methotrexate, reflecting the results obtained in clinical practice, and relatively sensitive to dianhydrogalactitol.

Animals

Increased SCE inducibility by low doses of methylcholanthrene in lymphocytes obtained from patients with Down's disease.

The inducibility of sister-chromatid exchanges (SCEs) following 3-methylcholanthrene (MC) treatment of normal human peripheral blood lymphocytes and of in vitro cultured normal human embryo fibroblasts, as well as peripheral blood lymphocytes of patients with Down's disease and of fibroblasts of an embryo with trisomy 21 has been investigated. 10(-6) M MC treatment increased the frequency of SCEs by 2.5 in the case of Down lymphocytes when compared to the healthy control. The fibroblasts with trisomy 21, however, did not show an increased sensitivity to MC treatment when compared with normal fibroblasts, expressed in the number of SCEs per nucleus found in the cells.

Dose-Response Relationship, Drug

Characterization of an adenylate cyclase system sensitive to histamine H2-receptor excitation in cells from dog gastric mucosa.

A method of preparing viable cells from dog gastric mucosa is described. Cyclic AMP in these cells is elevated by histamine and 4-methyl histamine but 2-methyl histamine is only a weak agonist. The effects on cyclic AMP levels are inhibited competitively by metiamide and burimamide which give apparent KBvalues of 3.5x10-7 M and 2.3x10-6 M, respectively. These values are similar to those reported for other histamine H2-receptor systems. The H1-receptor antagonists, mepyramine and chlorpheniramine, have no inhibitory effect on the histamine induced elevation of cyclic AMP: promethazine inhibits the system but not by a competitive mechanism. It is concluded that the histamine stimulated adenylate cyclase system is probably located in the parietal cell component.

Adenylyl Cyclase Inhibitors

Genotoxic effects of occupational exposure in the peripheral blood lymphocytes of pesticide preparing workers in Hungary.

Venous blood samples of 240 donors including 33 industrial and 60 historical controls were investigated in order to assess the genotoxic risk of pesticide preparing workers manufacturing monochlorinated benzene in Hungary. Mutation frequencies were determined in the hypoxanthine-(guanine)-phosphoribosyl transferase genes located on the X chromosome. DNA repair capacity was estimated following hydroxyurea treatment with subsequent UV irradiation of separated lymphocytes. Smoking as confounding factor of genotoxicity was also taken into consideration. Mutation frequencies were increased among the workers exposed to monochlorinated benzene in correlation with the duration of working time, compared to the controls. Mutation frequencies were lower than expected among non-smoker, long-exposed workers. Smoking itself proved to be an effective confounding factor in the enhancement of point mutations in the case of long-exposed workers. Smoking, however, caused no significant increase in the mutation frequency among the controls, and did not influence the DNA repair capacity of any of the groups.

Adult