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Biomedical subjects

J Major

Publications and source records attributed to J Major.

At least 37 records · Page 2Linked to original sources

[Bicentric stereotaxic convergent-beam irradiation].

PURPOSE: Circular collimated X-ray beams rotated in various non-coplanar planes as commonly used in stereotactic linac-based radiotherapy are generating spherical dose distributions with typically steep dose gradients. In case of irregular, especially elongated lesions, this technique fails to conform the shape of the corresponding planning target volume, and a collimator aperture has to be selected which allows for an acceptable dose distribution only on the expense of an excess dose to a larger amount of normal tissue. Therefore we have investigated a bicentric irradiation technique with sequentially treating an elongated target volume over two separated isocenters. METHODS: For the computer simulation studies we used the planning system of the stereotactic unit SRS-200 by Philips. Selected combinations of different collimator aperture were examined systematically by varying the distance between the two isocenters. Dose distributions for a specially developed head-phantom were calculated and analysed. RESULTS: Optimization tables were generated taking into account the geometric quality criteria as well as the corresponding dose maxima. For a given size of the target volume, the appropriate parameters for the bicentric radiation treatment can be chosen. The calculated dose distributions turned out to be independent of the positioning of the two isocenters within the phantom. CONCLUSION: The optimization tables serve to select a set of starting values for the interactive planning process of an elongated target volume resulting in a significant decrease of the overall time for treatment planning of irregular shaped lesions.

Film Dosimetry↗

Monitoring of benzene-exposed workers for genotoxic effects of benzene: improved-working-condition-related decrease in the frequencies of chromosomal aberrations in peripheral blood lymphocytes.

The genotoxic effects of benzene were assessed in peripheral blood lymphocytes of 49 workers occupationally exposed to benzene (3-68.7 mg/m3 in the work environment) for 0-2, 2-10 and more than 10 years (10, 22 and 17 workers, respectively). Chromosomal aberrations, SCEs and UV-induced DNA synthesis were used as indicators of genotoxic effects. Most of the workers were followed up in 1991 and 1992, while the benzene concentrations were reduced to 1-18.4 mg/m3 air. Considered overall, in the "exposed" groups, the frequencies of chromosomal aberrations were significantly higher than in controls thus providing evidence for the clastogenic effects of benzene. However, there seems to be no correlation between aberration frequencies and the duration of prior exposure to benzene. In 1991 and 1992, when the benzene concentrations were brought down, there was a concomitant decrease in the frequencies of chromosomal aberrations; in 1992 the decrease reached one third to one half of the initial frequencies, values still higher than in the controls. With the other genotoxic end-points, the changes were small and not consistent.

Air Pollutants, Occupational↗

Chromosome aberration, sister-chromatid exchange, proliferative rate index, and serum thiocyanate concentration in smokers exposed to low-dose benzene.

Cytogenetical endpoints, i.e., chromosome aberration (CA), sister-chromatid exchange (SCE), and proliferative rate indexes (PRI), were measured in peripheral blood lymphocytes (PBL) of 42 workers exposed occupationally to low-dose benzene, and of 42 controls. The role of smoking habit as a confounding factor of genotoxic effects caused by occupational low-dose benzene exposure was also studied. The benzene concentrations in the ambient air samples varied from 3 to 20 mg/m3 (mean: 7 mg/m3). The continuous low-dose benzene exposure significantly increased the CA and SCE frequencies, but did not influence PRI. Smoking levels were characterized by subjective accounts and by serum thiocyanate concentrations (SCN). CA and SCE were not significantly increased in smokers compared to nonsmokers, but the differences were expressed to a greater extent in the case of measurement of SCN concentrations. Determination of SCN proved to be more objective in the assessment of genotoxic effects of smoking as a confounding factor of occupational low-dose benzene exposure.

Adult↗

Hypoxic induction of interleukin-8 gene expression in human endothelial cells.

Because leukocyte-mediated tissue damage is an important component of the pathologic picture in ischemia/reperfusion, we have sought mechanisms by which PMNs are directed into hypoxic tissue. Incubation of human endothelial cells (ECs) in hypoxia, PO2 approximately 14-18 Torr, led to time-dependent release of IL-8 antigen into the conditioned medium; this was accompanied by increased chemotactic activity for PMNs, blocked by antibody to IL-8. Production of IL-8 by hypoxic ECs occurred concomitantly with both increased levels of IL-8 mRNA, based on polymerase chain reaction analysis, and increased IL-8 transcription, based on nuclear run-on assays. Northern analysis of mRNA from hypoxic ECs also demonstrated increased levels of mRNA for macrophage chemotactic protein-1, another member of the chemokine superfamily of proinflammatory cytokines. IL-8 gene induction was associated with the presence of increased binding activity in nuclear extracts from hypoxic ECs for the NF-kB site. Studies with human umbilical vein segments exposed to hypoxia also demonstrated increased elaboration of IL-8 antigen compared with normoxic controls. In mice exposed to hypoxia (PO2 approximately 30-40 Torr), there was increased pulmonary leukostasis, as evidenced by increased myeloperoxidase activity in tissue homogenates. In parallel, increased levels of transcripts for IP-10, a murine homologue in the chemokine family related to IL-8, were observed in hypoxic lung tissue. Taken together, these data suggest that hypoxia constitutes a stimulus for leukocyte chemotaxis and tissue leukostasis.

Animals↗

Mitotic delay in peripheral blood lymphocytes and fibroblast cultures obtained from a child with Down's syndrome and from a healthy child.

Mitotic delay (MD) often occurs in cells of donors exposed in vivo to genotoxic agents. To investigate individual sensitivity with genetic background, author measured the 3-methyl-cholanthrene (MC)-induced MD in cultured human skin fibroblasts (FBs) and in peripheral blood lymphocytes (PBLs) obtained from a 4-year-old patient with Down's disease. Samples from a 10-year-old healthy subject served as controls. Skin samples were obtained during surgical intervention. The induced MD was calculated from the mitotic index (MI) which was expressed in per cent of the control; at various times up to 18 h after treatment. Cells were treated with 10(-7), 10(-6) and 10(-5) M MC (with S-9 liver homogenate). At passage 10, the average MI (+/- SE) was 8.32 +/- 0.43%, and 7.85 +/- 0.64% for the healthy and for the Down's FBs, respectively; and it was 4.89 +/- 0.59%, and 4.92 +/- 0.72% for the healthy and for the Down's PBLs, respectively. MD was characterized as 50% MI of control (MD50). The MD50 values were the most expressed when cells were treated with 10(-5) M MC. No difference was found in MD of healthy and Down's fibroblasts. For Down's lymphocytes, on the other hand, MD was approximately 30% longer than for healthy cells. This result agrees well the reported increased SCE and decreased DNA-repair data obtained in PBL of Down patients.

Case-Control Studies↗

A lipopolysaccharide-inducible macrophage gene (D3) is a new member of an interferon-inducible gene cluster and is selectively expressed in mononuclear phagocytes.

We previously reported the isolation and characterization of cDNA clones encoding novel lipopolysaccharide (LPS)-inducible mRNAs from murine peritoneal macrophages. We now present the complete coding sequence of a cDNA previously termed D3. Analysis of multiple clones from a murine macrophage cDNA library provided a complete cDNA sequence of approximately 1.6 kb. The corresponding RNA contains a single open reading frame encoding a hydrophilic protein composed of 425 amino acids and is characterized by a region including three perfect and two imperfect repeats of a seven-amino-acid sequence. Based on nucleotide and deduced amino acid sequence, this mRNA is a new member of a previously described multigene cluster of interferon-inducible genes termed the Mouse 200 series genes. This new sequence most closely resembles gene 204 because both D3 and 204 genes have segments containing the seven-amino-acid repeat sequence. The Mouse 202 and 204 genes, however, have an approximately 200-amino-acid carboxyl-terminal domain that is absent in the LPS-inducible macrophage-derived cDNA. In addition, D3, 202, and 204 can all be distinguished from one another by virtue of unique 3' noncoding regions 200-300 base pairs in length. The D3 unique sequence is largely restricted to the smallest of the three size classes of this gene family expressed in macrophages and is not detected in interferon- or platelet-derived growth factor-stimulated fibroblasts. Overall, three separate mRNAs have now been described, each of which has three or more of a possible seven nucleotide sequence domains. Although the function(s) of the members of this gene family remains unknown, the multiple forms inducible by diverse stimuli and their restricted cell type expression suggest diverse and important physiologic roles for their products in inflammation.

Amino Acid Sequence↗

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↗