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Biomedical subjects

M Perry

Publications and source records attributed to M Perry.

At least 55 records · Page 3Linked to original sources

Oxygen radical-mediated lung damage associated with alpha-naphthylthiourea.

Lungs were damaged with alpha-naphthylthiourea (ANTU) and various compounds were used to block its effect. Although the results are variable, superoxide dismutase, catalase and dimethylsulfoxide all protected against ANTU, indicating that OH radicals are responsible for this type of lung injury. Leukocytes do not appear to be required for the damage to occur; however, hydroxurea (given over 2 days) did block the ANTU damage when neutrophils were decreased to 1/2 normal values or when administered acutely. The free radicals may be generated by the cyclooxygenase pathway since ibuprofen blocked the ANTU damage, whereas blocking xanthine oxidase using allopurinol failed to prevent the lung damage.

Animals

Genomic organization and nucleotide sequence of two distinct histone gene clusters from Xenopus laevis. Identification of novel conserved upstream sequence elements.

We have performed a detailed analysis of the genomic organization and the nucleotide sequence of two distinct Xenopus laevis histone gene clusters totaling approximately 23.5 X 10(3) base-pairs. Each cluster contains at least one copy of each of the five histone genes. However, these genes are present in different arrangements within each cluster and different H1A, H2A and H2B proteins (variants) are encoded by the respective genes of each cluster. Southern blot analysis of genomic X. laevis DNA indicates that each cluster is a member of a distinct family of tandemly repeated histone gene clusters. A comparative analysis of the nucleotide sequences flanking the histone genes within these two clusters has revealed the presence of multiple conserved sequence elements that are specific for each histone gene class and located at preferred upstream positions. Several of these elements correspond to sequences that are known to be required for maximal transcription of the corresponding genes. Most of these sequence elements have not been identified previously, although we find that many of them are present at corresponding locations upstream of histone genes from other organisms. We suggest that the conserved upstream sequence elements may play an important role in the expression of histone genes in vivo.

Amino Acid Sequence

Metabolism of estradiol by true and pseudoperoxidases.

The activation of 14C-labeled estradiol by "true" and "pseudo" peroxidases to form conjugates and other products was compared in four model systems using H2O2, glutathione, Mn2+ or irradiated riboflavin. Albumin was used as acceptor except in the glutathione system. The binding of estradiol to glutathione in the presence of the true peroxidases, lacto- or uterine peroxidase (no H2O2 added), was also examined and the conditions shown to differ from those required with the pseudoperoxidases, microperoxidase or trypsin-digested cytochrome c. The conjugates were purified by chromatography after elution from Amberlite XAD-2 and the relative amounts of these products assessed by autoradiography. The ratio of steroid to glutathione in the main water-soluble metabolite formed with lactoperoxidase was found to be approx 1:1 in a double label experiment with [14C]estradiol and [3H]glutathione. It was also shown, using estradiol labeled with 3H in different positions of the steroid molecule, that lactoperoxidase acts non-specifically in catalyzing the formation of glutathionyl conjugates as indicated by the release of 3H2O. The possible role of peroxidase and glutathione in the metabolism of estrogens and in the formation of artifactual products is discussed.

Animals

Comparative autoradiographic study of parasite-host-cell cyclical relationship in lymphoblastoid cell lines infected with Theileria annulata and Theileria parva in vitro.

Cyclical interactions between intracellular schizonts of the Ankara and Hissar strains of Theileria annulata and the Muguga strain of T. parva and the parasitised host lymphoblasts have been studied autoradiographically by following the incorporation of (3H) thymidine into parasite and host cell nuclei, and also by quantitating the number of schizont nuclei per lymphoblast, at various stages and phases of host cell cycle. The synthesis of DNA by Theileria schizonts and the parasitised host lymphoblasts was found to be asynchronous and to occur at different phases of the host cell interphase stage. While the lymphoblast nuclear DNA incorporates (3H) thymidine during the S phase, schizont nuclei were labelled during the G2 phase of the host lymphoblast interphase stage. The replication of schizont nuclei took place before the metaphase stage of host cell cycle, viz, prometaphase, so that the mean schizont nuclear number at host prometaphase and at anaphase--telophase was consistently more or less double the mean nuclear number at interphase.

Animals

Anti-IgG combined with rate nephelometry for measuring polyethylene glycol-precipitated circulating immune complexes.

Immune complexes from serum were assayed for IgG by a simple rate-nephelometric method after extraction with polyethylene glycol that removes monomeric IgG. A 30-min preincubation of the extracted material in reaction buffer before the anti-IgG is introduced eliminates falsely increased values owing to precipitation that increased baseline light scatter in the reaction buffer. We found good parallelism in the reaction of anti-IgG with the IgG calibrator, aggregated human globulin, or endogenous immune complex. Thus IgG can be used for calibration in place of aggregated human globulin, greatly simplifying the assay. A good correlation was found between the present assay and the C1q-binding test (r = 0.83). The present assay is both sensitive and reproducible. The extraction and assay are straightforward and can be completed in a single morning after an overnight precipitation. The reagents for extraction are easily prepared and inexpensive, and the materials for assay are available in kit form. We believe this approach to be well suited for many clinical laboratories to measure circulating immune complexes.

Antigen-Antibody Complex

The effect of histone hyperacetylation on the nuclease sensitivity and the solubility of chromatin.

We have examined the effects of histone hyperacetylation upon nuclease digestion of nuclei and subsequent fractionation of chromosomal material in the presence of MgCl2. DNase I shows a maximum sensitivity towards hyperacetylated nuclei at somewhat elevated ionic strengths (150-200 mM NaCl), whereas micrococcal nuclease exhibits no specificity for acetylated nuclei over a broad range of ionic strengths. Fractionation in the presence of MgCl2 of hyperacetylated nuclei digested with micrococcal nuclease results in a substantial increase in the amount of soluble chromatin relative to that obtained with control nuclei. This increased yield of Mg2+-soluble chromatin results from the recruitment into this fraction of oligonucleosomes containing extremely hyperacetylated histones. These results suggest that contiguous nucleosomes containing highly acetylated histones may be altered in their ability to interact with themselves and with other nucleosomes.

Acetylation

Oedeme bleu: a reappraisal.

The case-histories of four patients with self-induced lymphoedema show a distinctive organic syndrome, but the underlying mental mechanisms in these patients show no common thread other than an apparent wish to draw attention to an untreatable condition. A policy of non-intervention may reduce or limit the eventual disability.

Adult

Histone deacetylation in nuclei isolated from hepatoma tissue culture cells. Inhibition by sodium butyrate.

Nuclei from hepatoma tissue culture (HTC) cells were isolated by standard methods and incubated in media commonly used for nuclease digestions (DNAase I and micrococcal nuclease) and for in vitro RNA synthesis. During the incubation, histones can be deacetylated from both control cells and cells treated with 6 mM sodium butyrate to enhance the levels of histone acetylation. Deacetylation of histone is much more apparent in nuclei isolated from sodium butyrate-treated cells. Inclusion of 6 mM sodium butyrate in the incubation medium effectively inhibits the endogenous deacetylase activity acting on histones H3 and H4, whereas sodium acetate at the same concentration has very little inhibitory effect.

Acetates

Additional properties of a soluble polymer of glucose from cultures of Acetobacter xylinum.

The results of differential, thermal analysis of a soluble, beta (1 leads to 2)-branched, beta (1 leads to 4)-D-glucan isolated from cultures of Acetobacter xylinum are consistent with previous conclusions about its structure. The O-acetyl content of the polymer is 8.3% which corresponds to a maximum substitution of one acetyl group per three glucose residues. Proton nuclear magnetic resonance spectra confirm that all the glycosidic bonds are beta linkages. Some preparations of the polymer are contaminated by another polymer containing mannose and rhamnose. No evidence was obtained to support a previous suggestion that the branched D-glucan is a precursor of bacterial cellulose and this suggestion is now withdrawn.

Glucans

Thyroid function in patients with breast cancer.

Thyroid function has been assessed in 40 patients with breast cancer and compared with an age-matched control female population. The free thyroxine index was lower and the level of thyroid-stimulating hormone in the serum higher in the cancer group and these changes became more marked at 6 months. It is concluded that patients with breast cancer show more evidence of hypothyroidism as time progresses.

Breast Neoplasms

How it is at 84.

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Aged

Malignant neoplasms in the families of patients with ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is an autosomal recessive syndrome associated with a greatly increased incidence of malignant neoplasms in homozygous affected individuals. Heterozygotes for the gene for A-T are thought to comprise about 1% of the general population and, therefore, it is important to know whether this gene also predisposes the heterozygous carrier to cancers. Heterozygous carriers of this gene are common among the close relatives of patients with A-T, although individual carriers cannot be identified by any clinical criterion or laboratory test. For this reason, we compared the incidence of death from malignant neoplasms in 2 families of patients with A-T to that expected in a random sample of the general population. There were 59 deaths from malignant neoplasms in relatives dying before age 75, compared to 42.6 expected (p less than 0.02). For A-T heterozygotes younger than age 45, the risk of dying from a malignant neoplasm was estimated to be greater than 5 times the risk for the general population. A-T heterozygotes may comprise more than 5% of all persons dying from a cancer before age 45. The incidence of ovarian, gastric, and biliary system carcinomas and of leukemia and lymphoma was increased in these A-T families. Other neoplasms that may be associated with this gene in heterozygotes include pancreatic, basal cell, colonic, breast, and cervical carcinomas.

Ataxia Telangiectasia

Intestinal absorption following small-bowel resection.

Proximal or distal small-bowel resection was performed on female Wistar rats. Water, glucose, electrolyte, and bile acid absorption from the perfusate was studied in bile-fistula sham-operated rats and in animals 3 months after intestinal resection, using an in-vivo recirculation perfusion system. The jejunum and caecum, but not the colon, showed adaptive increases in intestinal absorption after resection of the ileum, and supranormal bile acid absorption and enhanced glucose, water, and electrolyte absorption were demonstrated in the ileum after jejunal resection. The improvement in diarrhoea observed in some patients after right hemicolectomy may be due to compensatory changes in the residual colon; rectal mucosal thickness becomes significantly increased after right hemicoletomy.

Animals