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Biomedical subjects

D G Lowe

Publications and source records attributed to D G Lowe.

At least 109 records · Page 6Linked to original sources

The role of vaginal scan in measurement of endometrial thickness in postmenopausal women.

Transvaginal ultrasound scanning was performed on 111 postmenopausal women. Of these women, 103 had postmenopausal bleeding, and eight were undergoing hysterectomy. Of the 103 women with bleeding, 93 had dilatation and curettage (D&C) and 10 patients were treated conservatively with a repeat scan in six months. A correlation of ultrasound findings and endometrial histopathology was possible in 94 patients. In 59 of these (63%) the endometrium was atrophic and the ultrasound endometrial thickness was 5 mm or less. In 29 (31%) patients the endometrial histology was abnormal and ultrasound endometrial thickness was greater than 5 mm. In six patients the endometrium was atrophic, but the ultrasonic endometrial thickness was apparently greater than 5 mm due to intracavity fluid. We suggest that an endometrial thickness of 5 mm is an appropriate cut-off level for conservative management of patients with postmenopausal bleeding, or in screening for endometrial carcinoma.

Aged↗

Differential regional expression of three natriuretic peptide receptor genes within primate tissues.

The natriuretic peptide receptors are three homologous cell surface proteins, each with a single transmembrane domain. The atrial natriuretic peptide receptor type A (ANPRA) and the homologous receptor type B (ANPRB) are both membrane guanylyl cyclases that synthesize cyclic GMP as an intracellular second messenger. The third receptor in this family, the atrial natriuretic peptide receptor type C (ANPRC), is not coupled to cyclic GMP production. We report on the distribution of the ANPRA, ANPRB, and ANPRC mRNAs in rhesus monkey tissues assayed by in situ hybridization. ANPRA mRNA is most abundantly expressed in the kidney glomerulus, adrenal zona glomerulosa, pituitary, cerebellum, and endocardial endothelial cells of the right and left atrium and right ventricle. In contrast, abundant ANPRB expression appears to be confined to the adrenal medulla, pituitary, and cerebellum. ANPRC mRNA appeared to be expressed very differently than ANPRA and ANPRB. In the heart, ANPRC mRNA is expressed most prominently in endocardial endothelial cells of all four chambers but is also found throughout the myocardium only in the right atrium. These data identify major sites of natriuretic peptide receptor mRNA expression and suggest that there may be prominent cell type-specific differential distribution of these receptors in central and peripheral targets for the natriuretic peptides.

Adrenal Cortex↗

Constitutive expression of leukemia inhibitory factor RNA by human bone marrow stromal cells and modulation by IL-1, TNF-alpha, and TGF-beta.

Recent in vitro studies indicate that bone marrow mesenchymal elements, residing in close proximity to hematopoietic cell populations, elaborate a network of cytokines that are, at least partially, responsible for modulating the growth and maturation of the latter compartment. Leukemia inhibitory factor (LIF), a molecule with both positive and negative regulatory activities, has been implicated in murine embryogenesis and hematopoiesis. We demonstrate that cultured normal human bone marrow stromal cells constitutively express LIF message. Further, exposure of these cells to other hematopoietic modulators including interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) (but not interferon-alpha [IFN alpha]) increases the level of LIF RNA. Interestingly, cultured stromal cells derived from three of four patients with chronic myelogenous leukemia showed enhanced LIF expression. These observations suggest that LIF may participate, either alone or through interaction with other cytokines, in the bone marrow microenvironment-mediated influence on both normal and malignant hematopoietic processes.

Bone Marrow↗

Inhibition of development of Na(+)-dependent hexose transport in renal epithelial LLC-PK1 cells by differentiation-stimulating factor for myeloid leukemic cells/leukemia inhibitory factor.

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor is a cytokine inducing differentiation of mouse myeloid leukemic M1-T22 cells. The effect of recombinant human D-factor on growth and differentiation of pig kidney LLC-PK1 cells was examined. LLC-PK1 cells did not concentrate alpha-methylglucoside during their early growth in culture but developed the capacity to concentrate this hexose as they reached confluence and their growth rate decreased. Purified D-factor caused dose-dependent inhibition of the development of this concentrative capacity. It did not affect the growth rate of the cells, but inhibited the formation of multicellular domes in confluent cultures. LLC-PK1 cells were found to have high-affinity binding sites (831 per cell) for D-factor with a dissociation constant of 197 pM.

Alkaline Phosphatase↗

Radioimmunoscintigraphy of ovarian tumors using a new monoclonal antibody, SM-3.

Radioimmunoscintigraphy with SM-3 monoclonal antibody produces results similar to those obtained with 123I-labeled HMFG-2. The tumor specificity of SM-3 in vitro is not as marked as that in vivo. SM-3 is, however, much easier to produce in tissue culture and, with the availability of 99mTc labelling, has allowed radioimmunoscintigraphy to be done as an outpatient procedure. This technique has important implications for the continuing management of patients with ovarian cancer.

Adult↗

Chromosomal distribution of three members of the human natriuretic peptide receptor/guanylyl cyclase gene family.

Chromosomal localization of the genes encoding three homologous human proteins, the ANPRA, ANPRB, and ANPRC cell surface receptors, was determined by polymerase chain reaction (PCR) analysis of genomic DNA from somatic cell hybrids. The ANPRA gene was assigned to 1q12----qter by intron-specific PCR. The ANPRB gene was assigned to 9p11----p22 using species-specific length variation in PCR fragments. The ANPRC gene was assigned to chromosome 5 using human-specific PCR primers identified by screening a human primer panel on parental DNA samples (shotgun primer screening). Chromosomal assignments based on PCR analysis were confirmed and the genes further sublocalized by in situ hybridization of cloned cDNA probes to human metaphase chromosomes. The ANPRA gene was sublocalized to 1q21----q22, the ANPRB gene to 9p12----p21, and the ANPRC gene to 5p13----p14.

Animals↗

Retroperitoneal soft tissue sarcomas: a review of the literature.

The English language literature on retroperitoneal sarcomas published between 1981 and 1988 has been reviewed. The histology, different prognostic factors, value of imaging techniques, and need for multidisciplinary management are discussed. Complete surgical excision with tumor-free margins confirmed by histology is essential if long-term survival and local control are to be achieved. In many cases resection of adjacent organs is required as most patients present with advanced, aggressive local disease. The roles of adjuvant radiotherapy and chemotherapy in the treatment of retroperitoneal sarcomas are uncertain and must await further controlled, randomized, prospective studies.

Diagnosis, Differential↗

Tissue preparation for simultaneous flow cytometric quantitation of tumour associated antigens and DNA in solid tumours.

A multiparameter flow cytometric assay for the simultaneous study of tumour associated antigens (TAA) and DNA in fresh solid tumours was devised. Cell suspensions were prepared by disaggregating unfixed solid tumour samples mechanically over a stainless steel mesh. Indirect immunofluorescence was used to identify the TAA, and DNA was stained with propidium iodide. Cell morphology was well preserved, cell clumping was negligible, and high quality indirect immunofluorescence quality indirect immunofluorescence and DNA staining were obtained. The technique is simple, rapid, and reproducible. Multiparameter assays can be developed to study prognostic indicators such as membrane oncoproteins, receptors, and multidrug resistance in solid tumours. With a suitable panel of antibodies the technique might become an aid in the differential diagnosis and biochemical diagnosis of some solid tumours.

Antigens, Tumor-Associated, Carbohydrate↗

Endothelial interleukin-8: a novel inhibitor of leukocyte-endothelial interactions.

Certain inflammatory stimuli render cultured human vascular endothelial cells hyperadhesive for neutrophils. This state is transient and reversible, in part because activated endothelial cells secrete a leukocyte adhesion inhibitor (LAI). LAI was identified as endothelial interleukin-8 (IL-8), the predominant species of which is an extended amino-terminal IL-8 variant. At nanomolar concentrations, purified endothelial IL-8 and recombinant human IL-8 inhibit neutrophil adhesion to cytokine-activated endothelial monolayers and protect these monolayers from neutrophil-mediated damage. These findings suggest that endothelial-derived IL-8 may function to attenuate inflammatory events at the interface between vessel wall and blood.

Amino Acid Sequence↗

Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases.

Alpha atrial natriuretic peptide (alpha-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60-70,000 (60-70 K), which is not coupled to cGMP production and may function in the clearance of ANP and the ANP-A receptor of Mr 120-140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human alpha-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.

Amino Acid Sequence↗

A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor.

Atrial natriuretic peptide (ANP) is a polypeptide hormone whose effects include the induction of diuresis, natriuresis and vasorelaxation. One of the earliest events following binding of ANP to receptors on target cells is an increase in cyclic GMP concentration, indicating that this nucleotide might act as a mediator of the physiological effects of the hormone. Guanylate cyclase exists in at least two different molecular forms: a soluble haem-containing enzyme consisting of two subunits and a non-haem-containing transmembrane protein having a single subunit. It is the membrane form of guanylate cyclase that is activated following binding of ANP to target cells. We report here the isolation, sequence and expression of a complementary DNA clone encoding the membrane form of guanylate cyclase from rat brain. Transfection of this cDNA into cultured mammalian cells results in expression of guanylate cyclase activity and ANP-binding activity. The ANP receptor/guanylate cyclase represents a new class of mammalian cell-surface receptors which contain an extracellular ligand-binding domain and an intracellular guanylate cyclase catalytic domain.

Amino Acid Sequence↗