Twenty-nine patients with a positive antimitochondrial antibody titer greater than or equal to 1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer greater than or equal to 1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.

Adult↗

PubMedDate not supplied

Therapeutic manipulations in uremic bleeding.

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Blood Transfusion↗

PubMedDate not supplied

Post-partum haemorrhage is associated with poor housing, not multiparity, in Botswana.

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Botswana↗

PubMedDate not supplied

The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice.

The antioxidant pyrrolidinedithiocarbamate improves the therapeutic efficacy of 5-fluorouracil (5-FU) against HCT-15 colorectal cancer cell line xenografts in nude mice without increasing toxicity to normal intestinal or hematopoietic tissues. In the current study we have shown that a similar clinically licensed antioxidant, N-acetylcysteine (200 mg/kg), can modulate the activity of 5-FU (120 mg/kg) against HCT-15 tumor xenografts in nude mice. We demonstrate that this effect is accompanied by a sustained elevation in p53-independent apoptosis without accompanying alterations in cell cycle kinetics. Extensive tumor necrosis is also a prominent feature of treatment; however, no significant impairment of neovascularization as assessed by intratumor microvessel density occurred. We believe that the clinical efficacy of N-acetylcysteine as an adjunct to 5-FU in advanced colorectal cancer should be investigated further.

Acetylcysteine↗

PubMedDate not supplied

Detection of a novel human class II HLA antigen.

Genetic, molecular and cellular analyses of the HLA-D region of the major histocompatability complex (MHC) in man have led to the definition of three different products. Two of these, DR and MB (the latter also known as DC (ref. 1) and LB-E (ref. 2)) are defined with serological reagents; the third, known as SB (ref. 3) and PL-3 (ref. 4) is defined with primed lymphocyte typing (PLT) cells. The classical features attributed to HLA-D region encoded (class II) molecules are that they are cell-surface dimers consisting of a structurally conserved alpha-chain noncovalently associated with a polymorphic beta-chain and that they are found primarily on B lymphocytes, some monocyte populations, endothelial and certain other cells. Using these criteria a monoclonal antibody, B7/21, was described as reactive with HLA-DR (ref. 7). We have now re-evaluated B7/21 antibody reactivity using mutant lymphoblastoid cell lines. It appears that this antibody does not react with the molecularly defined D region products described to date but instead, recognizes a class II antigen with distinctive molecular characteristics. We provisionally refer to this antigen as FA.

Antibodies, Monoclonal↗

PubMedDate not supplied

Immunization against SIVmne in macaques using multigenic DNA vaccines.

All structural and regulatory genes of SIVmne were cloned into mammalian expression vectors to optimize expression in vitro and immunogenicity in mice. Macaca fascicularis were immunized four times with plasmid DNA (n = 4), or two DNA priming inoculations followed by two boosts of recombinant gp160 plus Gag-Pol particles (n = 4). Following intrarectal challenge with SIVmne, all macaques became infected. Three monkeys immunized with DNA alone maintained low plasma virus loads by 1 year post-challenge; the fourth exhibited high virus loads and significant CD4+ cell decline. Two of the DNA plus boost and three control macaques had high virus loads and associated CD4+ cell decline. Both vaccine protocols elicited antibodies and comparable helper T-cell proliferative responses to gp160. Cytokine mRNA levels in activated peripheral blood mononuclear cells (PBMC) taken at time of challenge suggested a dominant T helper (Th) 1 state in three DNA-immunized and one protein-boosted macaque, which correlated with low virus loads and high CD4+ cell counts post-challenge.

AIDS Vaccines↗

PubMedDate not supplied

How to make a blastocyst.

Several of the new reproductive technologies have been cultivated from our current understanding of the genetic programming and cellular processes that are involved in the major morphogenetic events of mammalian preimplantation development. Research directed at characterizing the patterns of gene expression during early development has shown that the embryo is initially under maternal control and later superseded by new transcriptional activity provided by the activation of the embryonic genome. Several embryonic transcripts encoding: (i) growth factors, (ii) cell junctions, (iii) plasma membrane ion transporters, and (iv) cell adhesion molecules have been identified as contributing directly to the progression of the embryo through the preimplantation interval of development. In this brief review, we have outlined the patterns of expression and the integral roles that these gene families play in the morphogenetic events of compaction and cavitation. Research of this type has greatly facilitate our understanding of the control processes that underlie preimplantation development and represent but one area of this exciting and vigorous field of research.

Animals↗

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Epidermal growth factor receptors in colorectal carcinoma.

Nineteen samples of primary colorectal carcinoma and adjacent mucosa were examined for EGFr expression using radioligand binding assays and immunohistochemical staining with the monoclonal antibody EGFR1. Radioligand binding experiments showed expression of EGFr in both tumour and mucosa in all cases. In tumour samples EGFr levels ranged between 4 and 79 fmole per mg membrane protein (Kd = 0.1-0.4 X 10(-9) M). There was no significant difference in the level of EGFr expression between tumour and mucosa overall. Immunohistochemical staining with the EGFR1 antibody was useful in localising EGFr to epithelial elements although it was less sensitive than ligand binding assays.

Adenocarcinoma↗

PubMedDate not supplied

Saphenous vein graft aneurysms demonstrated by computed tomography.

A case of aneurysms of saphenous vein coronary artery bypass (CAB) grafts is presented with CT and echocardiography findings. Aneurysms of the bypass graft are rare complications of CAB surgery but many occur due to atherosclerosis, infection, surgical technique, or vasculitis.

Adult↗