A highly conserved intronic sequence is involved in transcriptional regulation of the alpha 1(I) collagen gene.

The first intron of the human alpha 1(I) collagen gene contains a positive, orientation-dependent cis-acting sequence located between bases +292 and +670. Transient transfection experiments indicate that this sequence is functional in both primary chicken tendon fibroblasts and in a human fibroblast-like cell line derived from SV40-transformed marrow stromal cells. DNase I footprint, methylation interference, and mobility shift analyses provide evidence for a sequence-specific binding activity and show that the region of binding corresponds to a 29-base-pair sequence that is also present in the rat alpha 1(I) collagen intron.

Cytokine receptors and B cell functions. I. Recombinant soluble receptors specifically inhibit IL-1- and IL-4-induced B cell activities in vitro.

IL-1 and IL-4 are important mediators of B cell growth and differentiation. The cell-surface receptors for these cytokines have recently been cloned and recombinant soluble receptors have been produced that bind their respective ligand. The ability of soluble forms of the murine IL-1R (sIL-1R) and IL-4R (sIL-4R) to inhibit B cell functions in vitro was examined.

Mesoderm induction by fibroblast growth factor in early Xenopus development.

In early amphibian development the mesoderm is formed around the equator of the blastula in response to inductive signals from the endoderm. At the time of its formation the mesoderm consists of a large 'ventral type' zone and a small 'organizer' zone. A screen of candidate substances showed that a small group of heparin binding growth factors (HBGFs) were active as mesoderm inducing agents in vitro.

Prenatal diagnosis of Conradi's syndrome. Case report.

A case is described of the diagnosis by ultrasound scanning during the second trimester of Conradi-Hünermann's syndrome (asymmetrical rhizomelic limb shortening or chondrodysplasia calcificans punctata). The prenatal diagnosis of limb shortening deformities is discussed.

BALB/cAn B cells and T cells have distinct susceptibilities to cytotoxic effects of snake venom.

Previous studies have analyzed abilities of snake venoms to preferentially kill certain animal cells. Some studies have examined selective cytotoxic effects of snake venoms on B and T lymphocytes, but few studies have determined abilities of snake venoms to interact with B and T cells at distinct stages of cellular development. Thus, this study has analyzed susceptibilities of immature and mature BALB/cAn splenic B cells and T cells to cytotoxic effects of crude venoms of snakes belonging to the families of Crotalidae, Elapidae, and Viperidae.

Relationship between the pharmacokinetics and toxicity of mitozolomide.

The cytotoxic drug mitozolomide has been found to cause unpredictably severe thrombocytopenia during phase I and II clinical trials. In an attempt to relate dose and pharmacokinetic parameters to toxicity, we measured plasma concentrations of mitozolomide in 14 patients with a range of malignancies. There were significant correlations (Spearman rank correlation test) between drug clearance and AUC and white blood cell nadir.

Characterisation of urinary metabolites of temozolomide in humans and mice and evaluation of their cytotoxicity.

The experimental antineoplastic agent temozolomide was not metabolised in vitro at a measurable rate by mouse liver fractions. In contrast, the temozolomide analogue 3-methylbenzotriazinone was metabolically N-demethylated by hepatic microsomes to yield benzotriazinone. The major route of excretion of [14C]-labelled temozolomide in mice was via the kidneys.

Molecular heterogeneity of interleukin-1 receptors.

Previous studies have shown that binding of IL-1 to its receptor and intracellular processing of the IL-1/IL-1 receptor complex appear to be different in B- and T-cells. The current report summarizes recent studies from our laboratory that show that the murine and human IL-1 receptors present on T-cells and fibroblasts are identical in primary sequence within each species, and highly similar even when the two species are compared. At present no cDNA clones have been isolated for IL-1 receptors present on B-cells.

The preferential effects of chloroquine on the IgM and IgG subclass responses to TI and TD antigens in BALB/cAn mice.

This study has determined the effects of chloroquine on the IgM and the IgG subclass responses of BALB/cAn mice to both thymus-independent (TI) and thymus-dependent (TD) antigens, and has found that in antigen-unprimed BALB/cAn mice chloroquine adversely affects antibody responses to both TI and TD antigens. However, in antigen-primed mice the immune responses to TD antigens were unaffected by chloroquine. The IgGl subclass response, but not necessarily other IgG subclass or IgM responses to TI and TD antigens, was adversely affected by chloroquine in unprimed mice only.

Growth factors as inducing agents in early Xenopus development.

Factors from two growth factor families have been identified as having mesoderm inducing activity. These include activin and TGF beta 2 from the TGF beta superfamily, and all members of the fibroblast growth factor (FGF) family. When isolated ectoderm explants are treated with any of these factors, a proportion of their cells are caused to differentiate into mesodermal tissue types instead of epidermis.

Severity of disease induced by a pancreatropic Coxsackie B4 virus correlates with the H-2Kq locus of the major histocompatibility complex.

Coxsackie B viruses are known etiological agents of pancreatic diseases, including diabetes. The pathogenesis of these infections is influenced by both host and viral factors. In this report, we examined whether the outcome of Coxsackie B4 virus infection is dependent on the genes within the major histocompatibility complex (MHC).

IL-1 induces rapid phosphorylation of the IL-1 receptor.

The IL-1R on murine T cells is a Mr = 80,000 plasma membrane glycoprotein. cDNA cloning and transfection experiments have shown that this is an integral membrane protein, which binds both IL-1 alpha and IL-1 beta and transduces the IL-1 signal. A mAb, RM-5, which binds an epitope on the receptor which is distinct from the IL-1 binding site has been produced in rats.

Application of the MultiScreen system to cytokine radioreceptor assays.

Radioreceptor assays are becoming increasingly valuable in the biotechnology community for a variety of basic and applied research applications. It is clear, for example, that assessing the potential spectrum of biological activities of a novel polypeptide regulatory factor can be greatly simplified by the development of a rapid radioreceptor assay, since a wide variety of cell types can be screened using a single type of assay. By contrast, searching for potentially diverse biological effects can be an extremely time-consuming process.

Competition for survival between motor units in mouse skeletal muscle.

The soleus nerve on one side of neonatal mice was crushed and the soleus muscle on the same side was surgically reduced in size. Some animals also had their lumbar spinal nerve 5 (L5) cut and misdirected in the same operation. Three months later, the number of L5 and L6 soleus motor units in the operated muscles was counted electrophysiologically and the number of muscle fibers was counted histologically.

Percutaneous transluminal coronary angioplasty: update 1988.

This report updates the current indications, techniques and investigational devices used in a busy interventional cardiology practice. Specific attention is devoted toward the problem areas of thrombolytic treatment of acute myocardial infarction, restenosis after angioplasty and the use of angioplasty in the treatment of multivessel coronary artery disease.

Evidence for different interleukin 1 receptors in murine B- and T-cell lines.

Previous studies have shown that binding of interleukin 1 (IL-1) to its receptor and intracellular processing of the IL-1/IL-1 receptor complex appear to be different in B- and T-lymphocyte cell lines. In this study we used a B-lymphoid cell line, 70Z/3, and T-lymphoid cell line, EL-4 6.1 C10, to explore further the differences that exist between IL-1 receptors on cells of B and T lineage.

Metabolism and murine pharmacokinetics of the 8-(N,N-dimethylcarboxamide) analogue of the experimental antitumor drug mitozolomide (NSC353451).

The in vitro cytotoxicity, stability, and metabolism of the 8-(N,N-dimethylcarboxamide) and 8-(N-methylcarboxamide) analogues of the experimental antitumor drug mitozolomide have been investigated in conjunction with their in vivo murine pharmacokinetics and metabolism. When tested against the TLX5 lymphoma in vitro the ID50 values for dimethylmitozolomide, methylmitozolomide, and mitozolomide were 14.6, 3.

Mesoderm induction by the mesoderm of Xenopus neurulae.

Combinations were made between explants of mesoderm from the archenteron roof of early Xenopus neurulae and explants of ectoderm from mid-blastulae. In each combination one component was labeled with the fluorescent lineage label RDA (rhodamine-dextran-amine). Frequent and large mesoderm inductions, consisting mainly of muscle, were found where the presomite plate was used as the inducer.

Clonal analysis of mesoderm induction in Xenopus laevis.

Acidic fibroblast growth factor (aFGF) has been used to induce mesoderm from single animal pole cells of midblastula stage Xenopus embryos. The cells are individually cultured in a completely defined medium and are able to differentiate as small clones in a high proportion of cases. FGF-treated cells can give rise to several mesodermal cell types, while untreated cells show only epidermal or neural differentiation.