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Biomedical subjects

M Fang

Publications and source records attributed to M Fang.

17 recordsLinked to original sources

[Changes in plasma interleukin-1 and their possible relationship with the changes in glucocorticoid receptor in aged long-distance runner].

For the study of the changes in plasma interleukin-1 (IL-1) and their possible relationship with the changes in glucocorticoid receptor (GR), plasma IL-1 and GR in peripheral blood leukocytes in aged long-distance runner were measured simultaneously. The activity of IL-1 was expressed as its ability to stimulate 3H-TdR incorporation in the thymocytes of C57 mice. GR was determined by whole cell assay with 3H-Dex. The results showed that the activity of plasma IL-1 in aged long-distance runner was 209%, 223% and 145% of the control at 14.7-18.7, 3.8-7.0 and 1.5-2.6 KD fractions. The GR in peripheral blood leukocytes in aged runner was 65% of the control. Possible relationship between the changes in IL-1 and GR in aged long-distance runner and its physiological significance are discussed.

Aged

Cellular immunosenescence: an overview.

Recent studies on space flights suggest that certain T cell immunologic activities are vulnerable to microgravitation. It would be desirable to know the extent to which these changes can be prevented or reversed. Since the changes observed are analogous to the effects of aging on immunity, a brief overview is presented of our current knowledge of age-related changes in immune cells and of the various interventional methods which have been used successfully in preventing the decline with age and in elevating the levels of immune functions of old individuals.

Aging

Induction of cytochrome P450 isozymes in human amnion FL cells and its application to the biological detection of mutagens.

Using AHH, EROD, ECOD and APND as marker enzymes and 3-MC, beta-NF, NE and PB as inducers, inducible cytP450 IA and IIB gene expression was demonstrated in the human amnion FL cell line; these cells possess a broad spectrum of drug-metabolizing enzymes. Maximum induction was observed following co-treatment with 3-MC and NE. Both constitutive and induced AHH were proved to have the characteristics of cytP448-dependent mixed-function oxygenases. Induced cytP450 isozyme activity remained at a high level for 24-36 h after removal of the inducer. The induced FL cells were demonstrated to activate common promutagens/procarcinogens in UDS and ADPRT-mediated decrease of NAD content assay systems. This new design can be used as a simplified mutagen screening system: no supplemental liver microsomal activation system is needed.

Amnion

Radioimmunodetection of degranulated human eosinophils in mice: a potential model for imaging Hodgkin's disease and other pathologic conditions.

Various human tumors such as lymphomas and carcinomas sometimes contain extensive infiltration by degranulating eosinophils. To determine if degranulated eosinophils are suitable targets for immunolocalization, we performed in vivo distribution and imaging studies in mice, using EOS (a murine monoclonal antibody directed to human eosinophil peroxidase) labeled with indium-111. Adult mice were injected intravenously with radiolabeled EOS antibody or with similarly radiolabeled normal mouse IgG before receiving an intramuscular injection into the right thigh of homogenized human eosinophils adsorbed to latex microspheres. There was striking localization in the right thigh of the radiolabeled EOS antibody detectable by gamma imaging techniques as soon as 24 hr after injection. By contrast, there was little accumulation of radiolabeled normal IgG in the right thigh. We conclude that human eosinophil peroxidase is potentially a suitable target for radioimmunodetection and therapy of neoplasms and pathologic conditions that contain degranulating eosinophils.

Animals

Detection of rare cells expressing shared lymphoma idiotypes in fetal spleens.

Monoclonal antibodies have been derived against the shared and private idiotypes of immunoglobulin expressed by human B-cell lymphomas. We performed indirect immunofluorescence assays on cells from 3 fetal spleens, 3 adult spleens and 10 hyperplastic lymph nodes with a panel of 5 monoclonal antibodies directed to private lymphoma idiotypes, 2 antibodies directed to shared lymphoma idiotypes and various positive and negative control antibodies. Rare (less than 5%) cells in the fetal spleens, adult spleens and hyperplastic lymph nodes reacted with the 2 antibodies directed to shared lymphoma idiotypes. No cells in any of the specimens were reactive with the antibodies directed to private lymphoma idiotypes. We conclude that rare cells expressing shared lymphoma idiotypes are present during fetal development and in mature lymphoid tissue. This suggests that shared lymphoma idiotypes are expressed as part of a developmental process rather than in response to a specific environmental antigen.

Adult

Analysis of genes coding for S-antigen, interstitial retinol binding protein, and the alpha-subunit of cone transducin in patients with retinitis pigmentosa.

We screened 526 unrelated patients with autosomal dominant, autosomal recessive, or simplex retinitis pigmentosa for evidence of mutations of the genes encoding S-antigen (S-Ag), interstitial retinol binding protein (IRBP), and the alpha-subunit of cone-specific transducin. Restriction fragment length polymorphisms (RFLPs) were identified at each of these loci. Within each set of patients with a particular genetic type of retinitis pigmentosa, RFLP alleles at each of these loci showed no departure from Hardy-Weinberg equilibrium. No gene deletions or rearrangements could be detected in any patient. Furthermore, in each of six pedigrees (one autosomal dominant, one autosomal recessive, three Usher's syndrome type I, and one Laurence-Moon-Bardet-Biedl syndrome) there was no co-segregation of the disease with alleles determined by RFLPs at the locus for S-antigen. At the IRBP locus, lack of co-segregation was seen in one autosomal dominant, two autosomal recessive, and three Usher's syndrome type I pedigrees. Finally, one pedigree with autosomal recessive retinitis pigmentosa showed no co-segregation of the disease with alleles at the locus for the alpha-subunit of the cone-specific transducin. These data support the idea that the genes coding for S-Ag, IRBP, and the alpha-subunit of the cone-specific transducin do not play an etiologic role in the families with retinitis pigmentosa so far studied.

Alleles

ADPRT-mediated decrease of cellular NAD content and the detection of chemically induced DNA damage--development of a new short-term screening test for mutagens.

It was found that the DNA-damaging agents N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl-methanesulphonate (MMS) and 4-nitroquinoline-N-oxide (4NQO) could stimulate ADP-ribosyl transferase (ADPRT) activity and reduce the cellular NAD content in a dose-dependent way. The reduction of NAD after DNA damage could be partially or completely prevented by ADPRT inhibitors, 3-aminobenzamide or nicotinamide, which showed no influence on reduction of NAD induced by metabolic blocking agents. Therefore, a simple and specific method to detect DNA-damaging mutagens by measuring ADPRT-mediated decrease of cellular NAD content was explored. Using beta-naphthoflavone, a mixed function oxygenase inducer, together with induced or uninduced human amnion FL cells, it was found that aflatoxin B1, benzo(a)pyrene, 2-acetylaminofluorene, 9,10-dimethylanthracene and ethylcarbamate could induce the ADPRT-mediated decrease of cellular NAD content, while 4-acetylaminofluorene, anthracene, isopropyl-N-(3-chlorophenyl)-carbamate, beta-propiolactone, gamma-butyrolactone, cyclophosphamide and safrol could not. The results indicate that this is a cheap and specific method to detect DNA damage caused by chemical carcinogens/mutagens with a specificity approaching that of the unscheduled DNA synthesis assay.

Amnion

On the relationship between adenosine diphosphoribosyl transferase and S phase DNA synthesis in cultured mammalian cells.

The cell cycle dependent fluctuation of adenosine diphosphoribosyl transferase (ADPRT) activity was demonstrated by both nicotinamide adenine dinucleotide (3H-NAD+) incorporation into the acid insoluble fraction of permeabilized cells and changes in the cellular content of NAD, the only substrate of ADPRT, in intact FL cells. The ADPRT activity was lowest in the G1 phase and highest in the S/G2-G2 phase. Aphidicolin, a specific inhibitor of DNA polymerase a, abolished the fluctuation of ADPRT activity. Meanwhile, in 5-fluorodeoxy-uridine (FUdR) exposed cells whose DNA synthesis was interfered with by the inhibition of thymidylate synthetase and the rate of ligation of short replicative intermediates, the ADPRT activity remained at a higher level than in controls. However, 3-aminobenzamide (3AB), a potent ADPRT inhibitor, showed down DNA synthesis in the S phase and also extended the S phase. These results indicate that ADP-ribosylation may be involved in DNA replication and cell cycle progression, and suggest that ADPRT activity may be stimulated by transient short fragments of newly replicated DNA, exerting its effects at the later stages of DNA replication, most probably at the ligation step of DNA synthesis.

Amnion

A persistent untranslated sequence within bacteriophage T4 DNA topoisomerase gene 60.

A 50-nucleotide untranslated region is shown to be present within the coding sequence of Escherichia coli bacteriophage T4 gene 60, which encodes one of the subunits for its type II DNA topoisomerase. This interruption is part of the transcribed messenger RNA and appears not to be removed before translation. Thus, the usual colinearity between messenger RNA and the encoded protein sequence apparently does not exist in this case. The interruption is bracketed by a direct repeat of five base pairs. A mechanism is proposed in which folding of the untranslated region brings together codons separated by the interruption so that the elongating ribosome may skip the 50 nucleotides during translation. The alternative possibility, that the protein is efficiently translated from a very minor and undetectable form of processed messenger RNA, seems unlikely, but has not been completely ruled out.

Amino Acid Sequence

Langerhans cells in connective tissue diseases.

We have conducted a quantitative analysis of Langerhans cells (LC) in skin biopsies of 20 patients with various connective tissue diseases. Clinically normal skin of SLE patients as well as lesional skin of DLE showed consistently normal LC densities as assessed using ATPase staining, anti-DR and anti-OKT6. Examination of LC in clinically involved skin of patients with scleroderma revealed an absolute or relative decrease in ATPase and OKT6 expression, while staining with anti-DR gave inconclusive results. Clinically normal skin of the same individuals showed basically normal LC density. These findings suggest that the perturbation of the LC population is probably an expression of a secondary local phenomenon, and does not reflect a more widespread derangement of the accessory cells in the skin.

Adenosine Triphosphatases

Fibrodysplasia ossificans progressiva: CT appearance.

Twelve patients with fibrodysplasia ossificans progressiva were studied with computed tomography (CT). Characteristic swelling of the muscular fascial planes could be identified on CT scans prior to the development of ectopic ossification. Ossification could be seen on CT scans before it was apparent on plain radiographs. The pattern of ossification was similar to that seen at pathologic study, with multifocal sites developing adjacent to and extending around muscles. The appearance on CT scans confirms the hypothesis that the initial focus in fibrodysplasia ossificans progressiva is in the connective tissue.

Adolescent

Echo-planar imaging of the central nervous system at 1.0 T.

Echo-planar imaging (EPI) on the authors' 1-T prototype imager provides high-quality 100-msec images of the central nervous system. Contrast parameters can be chosen freely. Three-dimensional EPI sequences provide isotropically resolved data sets with 1-mm resolution. Brain perfusion and blood-brain barrier disruption can be assessed in time-course studies with gadopentetate dimeglumine. The current state of development of the authors' midfield research EPI system is discussed and its image quality illustrated through selected patient studies.

Blood-Brain Barrier