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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 235 records · Page 13Linked to original sources
PubMed1990

Pancreatic beta-cell somatostatin receptors.

The characteristics of somatostatin (SRIF) receptors in rat pancreatic beta-cells were investigated using rat islets and the beta-cell line HIT-T15 (HIT). The biochemical properties of the SRIF receptors were examined with 125I-labeled des-Ala-1,Gly-2-desamino-Cys-3-[Tyr-11]- dicarba3,14-somatostatin (CGP 23996). 125I-CGP 23996 bound to SRIF receptors in HIT cells with high affinity and in a saturable manner. The binding of 125I-CGP 23996 to SRIF receptors was blocked by SRIF analogues with a rank order of potency of somatostatin 28 (SRIF-28) greater than D-Trp-8-somatostatin greater than somatostatin 14 (SRIF-14). To investigate the physical properties of the HIT cell SRIF receptor, the receptor was covalently labeled with 125I-CGP 23996 using photo-cross-linking techniques. 125I-CGP 23996 specifically labeled a protein of 55 kDa in HIT cell membranes. The size of the SRIF receptor in HIT cells is similar to the size of the SRIF receptor labeled with 125I-CGP 23996 in membranes of freshly isolated islets, suggesting that the physical properties of SRIF receptors in HIT cells and rat islet cells are similar. The binding studies suggest that beta-cells predominantly express a SRIF-28-preferring receptor. In freshly isolated islets, glucose- and arginine-stimulated insulin release was effectively blocked by SRIF-28 but not by SRIF-14. SRIF-14 did inhibit arginine-stimulated glucagon secretion from freshly isolated islets. The dissociation of the inhibitory effects of SRIF-28 and SRIF-14 on insulin and glucagon release from freshly isolated islets suggests that the two peptides act through different receptors in islets to regulate hormone secretion.

Animals↗
PubMed1990

Growth of the chick area vasculosa in ovo and in shell-less culture.

The rates of growth and cell proliferation of the chick area vasculosa (Days 2-5 of incubation) were examined in windowed eggs and in shell-less culture preparations. For embryos of developmental Stages 15 to 23, the area vasculosa in shell-less cultures was significantly smaller than in corresponding eggs; however there was no significant difference in the radial growth between these groups. The cultivation of embryos in shell-less culture did not affect the normal macroscopic or histological appearance of the membrane, or the rate of proliferation of its constituent cells, as assessed by tritiated thymidine incorporation. These results indicate that the area vasculosa in shell-less culture provides a suitable assay of factors which regulate angiogenesis.

Animals↗
PubMed1990

Acute central nervous system symptoms caused by ibuprofen in connective tissue disease.

We describe 2 cases of acute encephalopathy in patients with connective tissue disease caused by small doses of ibuprofen. In addition to aseptic meningitis, both patients had altered mental status and focal neurologic signs, ophthalmoplegia in one and hemiparesis in the other. The spectrum of neurologic manifestations of ibuprofen hypersensitivity is reviewed.

Acute Disease↗
PubMed1989

Vestibular system of the newborn marsupial cat Dasyurus hallucatus.

The ultrastructure of the ear of the newborn native cat was examined to determine whether the vestibular system contained sensory receptors. A sensory region, presumably the utricle, was identified in each ear and consisted of a discrete population of otoliths overlying a sensory epithelium which possessed kinocilia and stereocilia. The remainder of the vestibular system did not appear to be developed anatomically. The newborn cat has rudimentary vestibular, olfactory, and mechanoreceptors (Merkel cells), and these structures may aid the newborn marsupial in the journey from the urogenital sinus to the pouch and in locating the teat.

Animals↗
PubMed1989

Functional organization of cerebral microvasculature in a marsupial, the northern quoll (Dasyurus hallucatus).

Capillaries within the central nervous system (CNS) of eutherian mammals form meshworks with numerous anastomoses, whereas capillaries in the CNS of marsupials consist entirely of hairpin-like loops, without anastomotic interconnections. Counter-current blood flow in capillary loops may have been important in the evolutionary development of a cerebral vascular supply. However, loops are not found in eutherian mammals, perhaps because of a limited benefit to the diffusive conductance of gases.

Animals↗
PubMed1989

Activity of the pyrazoloacridines against multidrug-resistant tumor cells.

A series of 2-aminoalkyl-5-nitropyrazolo [3,4,5-kl]acridines (pyrazoloacridines) were tested in vitro against a panel of multidrug-resistant cell lines comprising Adriamycin-resistant P388 leukemia, B16 melanoma, and mammary adenocarcinoma 16c. This new class of anticancer agents, particularly the 9-substituted methoxy derivatives, exhibited significant activity against all of the lines tested. The degree of cross-resistance to these compounds ranged from zero to 8-fold in the 138-fold Adriamycin-resistant P388/ADR line and was greatly diminished in the B16/ADR and 16c/ADR lines. Selected pyrazoloacridines were subsequently tested in vivo against B16 and B16/ADR cells established as solid tumors from the tissue culture line and shown to retain a significant degree of Adriamycin resistance. Whereas the B16/ADR line exhibited 2 logs less net tumor-cell kill than the B16 parent in response to Adriamycin treatment, the resistant tumor was completely sensitive to the pyrazoloacridines tested and proved in some experiments to be collaterally sensitive. The favorable activity of the pyrazoloacridines against these Adriamycin-resistant tumor lines points to the potential efficacy of these compounds against multidrug-resistant tumors encountered clinically.

Acridines↗
PubMed1989

DNA sequence, structure, and phylogenetic relationship of the small subunit rRNA coding region of mitochondrial DNA from Podospora anserina.

DNA sequence analysis and the localization of the 5' and 3' termini by S1 mapping have shown that the mitochondrial (mt) small subunit rRNA coding region from Podospora anserina is 1980 bp in length. The analogous coding region for mt rRNA is 1962 bp in maize, 1686 bp in Saccharomyces cerevisiae, and 956 bp in mammals, whereas its counterpart in Escherichia coli is 1542 bp. The P. anserina mt 16S-like rRNA is 400 bases longer than that from E. coli, but can be folded into a similar secondary structure. The additional bases appear to be clustered at specific locations, including extensions at the 5' and 3' termini. Comparison with secondary structure diagrams of 16S-like RNAs from several organisms allowed us to specify highly conserved and variable regions of this gene. Phylogenetic tree construction indicated that this gene is grouped with other mitochondrial genes, but most closely, as expected, with the fungal mitochondrial genes.

Ascomycota↗
PubMed1989

DNA sequence and secondary structures of the large subunit rRNA coding regions and its two class I introns of mitochondrial DNA from Podospora anserina.

DNA sequence analysis has shown that the gene coding for the mitochondrial (mt) large subunit ribosomal RNA (rRNA) from Podospora anserina is interrupted by two class I introns. The coding region for the large subunit rRNA itself is 3715 bp and the two introns are 1544 (r1) and 2404 (r2) bp in length. Secondary structure models for the large subunit rRNA were constructed and compared with the equivalent structure from Escherichia coli 23S rRNA. The two structures were remarkably similar despite an 800-base difference in length. The additional bases in the P. anserina rRNA appear to be mostly in unstructured regions in the 3' part of the RNA. Secondary structure models for the two introns show striking similarities with each other as well as with the intron models from the equivalent introns in Saccharomyces cerevisiae, Neurospora crassa, and Aspergillus nidulans. The long open reading frames in each intron are different from each other, however, and the nucleotide sequence similarity diverges as it proceeds away from the core structure. Each intron is located within regions of the large subunit rRNA gene that are highly conserved in both sequence and structure. Computer analysis showed that the open reading frame for intron r1 contained a common maturase-like polypeptide. The open reading frames of intron r2 appeared to be chimeric, displaying high sequence similarity with the open reading frames in the r1 and ATPase 6 introns of N. crassa.

Ascomycota↗
PubMed1989

Bioenergetic response of pancreatic islets to stimulation by fuel molecules.

The relationship of fuel-stimulated insulin secretion and the beta-cell bioenergetic state was investigated in isolated rat islets. In islets perifused with 5 mmol/L glucose to maintain a high basal energy state, stimulation by 9 to 28 mmol/L glucose increased the [ATP]/[ADP] and [GTP]/[GDP]. The rise in the former occurred prior to, or coincident with, the onset of insulin secretion and was dependent on glucose concentration. The increase in the latter appeared to lag behind the alteration in the [ATP]/[ADP] and achieved statistical significance after 30 minutes of incubation. Addition of 20 mmol/L alpha-ketoisocaproic acid, a powerful secretagogue, also caused a rise in the [ATP]/[ADP]. By contrast, 20 mmol/L lactate, which affected insulin secretion only minimally, failed to alter nucleotide concentrations. These data support the hypothesis that an increase in the islet energy state is a metabolic signal linking fuel metabolism with initiation of insulin secretion.

Adenosine Diphosphate↗
PubMed1989

Caffeine taste test for panic disorder: adenosine receptor supersensitivity.

The present study introduces a novel measure of adenosine receptor sensitivity that is based on the action of specific receptor blockers (e.g., caffeine) to potentiate the ability to detect threshold quinine concentrations. The test is used to compare gustatory adenosinergic responses to caffeine challenges in normal controls and patients with panic disorder or posttraumatic stress disorder (PTSD). Panic disorder patients had an exaggerated response to the caffeine challenge that was not found in controls or PTSD patients, although the latter had higher anxiety scores on psychometric tests. The results are related to a model in which A1-adenosine receptors up-regulate in an attempt to modulate hyperactive excitatory neuronal systems.

Adult↗
PubMed1989

Growth-inhibitory and growth-stimulatory effects of epidermal growth factor on human breast cancer cell line, MDA.MB.436: dependence on culture conditions.

Epidermal growth factor (EGF) is growth inhibitory for some cell lines, especially those having over-expressed EGF receptors. We have examined the effects of murine EGF on the growth of the human breast cancer cell line, MDA.MB.436, which has low numbers of EGF receptors. In the presence or absence of serum a 6 day exposure to 0.1 ng/ml EGF causes inhibition of growth if the culture medium is left unchanged during the course of the experiment but the same concentration of EGF causes stimulation above control if the EGF-containing medium is replaced daily. A 1 day exposure to 0.1 ng/ml followed by return to control medium has no effect on subsequent growth. The cells do not synthesize EGF receptor binding activity and added EGF is degraded within 2 days, suggesting that the inhibitory effects of EGF persist in its absence.

Breast Neoplasms↗
PubMed1989

Epidermal growth factor promotes chick embryonic angiogenesis.

The response of the early extraembryonic vasculature to epidermal growth factor (EGF) was studied. Millipore filter discs containing 10ng-1 microgram of EGF were placed onto the advancing edge of the area vasculosa of 3-day chick embryos, and the effect examined macroscopically and histologically 24 hours after disc application. The capillary density at the site of application increased significantly, and the effect was seen to be dose-dependent; a similar but more marked response was observed in the vessel cross-sectional area per unit length. This change in vascularity was accompanied by tortuous folding of the mesoderm and endoderm (which normally lie parallel to the ectoderm in a trilaminar arrangement) into the yolk substance: this may indicate precocious development of all three layers (ectoderm, mesoderm and ectoderm) of the membrane, and the proliferative effects of EGF may not be confined to the vascular endothelium.

Angiogenesis Inducing Agents↗
PubMed1989

Parotid gland enlargement and xerostomia associated with labial sialadenitis in HIV-infected patients.

Infection with human immunodeficiency virus (HIV) may be associated with enlargement of the major salivary glands or symptoms of dry mouth. We term this condition HIV-associated salivary gland disease (HIV-SGD). In this report we describe 12 patients with HIV-SGD. Nine patients (one child, eight adults) had enlargement of the parotid glands, and three had xerostomia alone. Symptoms of dry mouth, dry eyes or arthralgia occurred in 11, five and five patients, respectively. Salivary flow rates were normal or slightly reduced in seven patients and severely reduced in five. Labial salivary gland (LSG) biopsy specimens from patients contained lymphocytic infiltrates in focal and other patterns, whereas specimens from three HIV-infected patients without salivary gland symptoms did not. The inflammatory infiltrates in LSG specimens showed a preponderance of T8-positive cells and a tissue T4/T8 average ratio of 0.66. The mean T4/T8 ratio of peripheral blood lymphocytes was 0.4. Serum antinuclear antibodies were present in one patient, but rheumatoid factor, SS-A, and SS-B antibodies were absent in all. Search for Epstein-Barr virus and cytomegalovirus in the LSG tissue of the six patients tested did not reveal evidence of antigens or DNA. HIV-SGD patients show a number of similarities to and differences from patients with Sjögren's syndrome (SS). The similarities include the oral and salivary features, histopathology and possibly changes in other organs. The differences include the lower salivary gland T4/T8 ratio and the absence of autoantibodies in serum. The causes of HIV-SGD as well as of Sjögren's syndrome are unknown.

Adult↗
PubMed1989

Characterisation of a tamoxifen-resistant variant of the ZR-75-1 human breast cancer cell line (ZR-75-9a1) and ability of the resistant phenotype.

A 6-month exposure of ZR-75-1 human breast cancer cells to tamoxifen (1 microM rising to 2 microM). resulted in a fall in oestrogen receptor (ER) levels from 225 fmol mg protein-1 to 56 fmol mg protein-1 while progesterone receptor (PGR) concentration fell from 63 fmol mg protein-1 to undetectable levels. Sensitivity to the anti-proliferative effects of tamoxifen was unchanged. A further 6 months' exposure to 4 microM tamoxifen resulted in loss of detectable ER and PGR and development of resistance to tamoxifen. Resistant cells, designated ZR-75-9a1, displayed morphological changes consistent with the acquisition of a less well differentiated phenotype. Flow cytometric studies demonstrated that the cell cycle distribution pattern of the resistant variant growing in the presence of 8 microM tamoxifen was identical to that of the untreated parent line, which showed marked accumulation of cells in G0/G1 when exposed to 8 microM tamoxifen. The resistant phenotype was not stable if cells were transferred to complete drug-free medium, but remained stable for at least 3 months in the presence of medium lacking oestrogenic activity. ZR-75-9a1 cells differ from previously reported tamoxifen-resistant variants of the MCF-7 line which retain ER and may prove a valuable model for the study of the development and stability of tamoxifen resistance in human breast cancer.

Breast Neoplasms↗
PubMed1989

Synthesis of somatostatin by breast cancer cells and their inhibition by exogenous somatostatin and sandostatin.

Three human breast cancer cell lines ZR-75-1, MDA-MB-436 and MCF-7 were found to contain respectively, 3.06, 2.69 and 1.86 fmol of somatostatin-like immunoreactivity (SLI) per 10(6) cells. Since SLI is undetectable in the passaging media it must, therefore, be synthesised by the cells. In the presence of fetal calf serum the cells were growth inhibited by addition of somatostatin or its long-lasting analogue, Sandostatin, but only after 3 days of continuous exposure. A 1-day exposure to either peptide had little or no effect on subsequent cell growth in peptide-free medium. Inhibition of cell proliferation is not due to cytotoxic effects of the dose used (500 ng ml-1, each) since both peptides caused short-term stimulation of growth in the absence of serum.

Breast Neoplasms↗