Search PubMed⌕ Search

Biomedical subjects

M Hardy

Publications and source records attributed to M Hardy.

At least 55 records · Page 3Linked to original sources

Characterization of two neuroblastoma cell lines expressing recombinant nerve growth factor receptors.

In earlier studies, a 75,000-dalton glycoprotein (gp75) has been identified as a component of both low- and high-affinity nerve growth factor (NGF) receptors (NGFRs). Using an amphoteric expression vector, we have introduced the cDNA encoding the human gp75 into two neuroblastoma cell lines. SHEP is a human neuroblastoma cell line that lacks most neuronal characteristics and does not express NGFRs. The transformant line SHEP/NGFR expressed a single affinity class of NGF binding sites, did not display NGF-induced up-regulation of fos oncogene expression, and did not efficiently internalize NGF. LAN5 is a neuroblastoma cell line with neuronal characteristics, including expression of neurofilament and display of short neurites. This cell line expresses a small number of high-affinity NGFRs but no detectable low-affinity sites. The transformant line LAN5/NGFR expressed both high- and low-affinity NGFRs, displayed NGF-induced up-regulation of fos oncogene, and efficiently internalized NGF. The number of high-affinity NGF binding sites was nearly the same for LAN5 and LAN5/NGFR, a finding suggesting that there is a limiting number of some separately coded factor or subunit that is required for high-affinity NGFRs. Because NGF induction of fos oncogene expression correlated with expression of high-affinity NGFRs, the putative second factor may also limit NGF responsiveness.

Binding Sites↗

Angioma fusiform cells stimulated by conditioned medium from melanoma cells secrete a neomatrix which plays a role in "in vitro metastasis".

The rebuilt tumor model is a three dimensional mass of tumoral cells and angioma fusiform cells in collagen. Rebuilt tumors can give rise to "in vitro metastases" and these metastases depend on the presence of a neomatrix secreted in vitro by rebuilt tumor cells. This study defines the origin of the neomatrix and its role in "in vitro metastasis". Fusiform cells of angioma origin (AF3cells) were stimulated ten-fold by growing them in conditioned medium from a human melanoma cell line (MM2). The stimulated AF3 cells produced a dense neomatrix that was firmly attached to the culture flask. The AF3 cells were removed and MM2 cells were grown on this neomatrix. They gave rise to tumorous nodules very like the "in vitro metastases" produced by rebuilt tumors. The MM2 conditioned medium contained basic fibroblast growth factor, which could account for the angiogenetic activity of the tumoral cells. The fusiform cells of angioma origin that are stimulated by cancerous conditioned medium, are responsible for secretion of the neomatrix which plays a role in "in vitro metastasis".

Culture Media↗

[Three-dimensional model of cancer and in vitro metastasis: application to non-Hodgkin malignant lymphoma].

In vitro cancer studies require models more appropriate than the standard monolayer cultures of tumoral cell lines. This report describes the production of an in vitro three-dimensional rebuilt tumor using a non-hodgkin malignant lymphoma. The model exploits the relationship between angiogenesis and cancer formation by employing both tumor cells and fusiform cells derived from an angioma. The significance of this model, which has also been used with malignant melanoma cells, is that the rebuilt tumor, when placed in culture, produces many tumorous nodules which are fixed to a sub-layer of fusiform cells and newly-secreted matrix. These are, in effect, in vitro metastases. The ultrastructural aspect of this neomatrix indicates its proteoglycan nature. The micro-environment formed by the vascular cells and matrix appears to be critical for the production of metastases.

Cell Line, Transformed↗

Sensitive blotting assay for the detection of glycopeptides in peptide maps.

A dot blotting assay using digoxigenin hydrazide (Glycan detection kit, Boehringer Mannheim Biochemicals) was used to screen an endoproteinase Lys-C peptide map of ribonuclease B for the presence of glycopeptides. The carbohydrate content of the identified glycopeptide fraction was then further characterized by monosaccharide analysis using high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). The tandem use of a hydrazide dot blotting technique to screen peptide maps for glycopeptides and subsequent use of HPAE-PAD to identify the monosaccharide composition of glycopeptide hydrolyzates proved to be a quick, sensitive and reliable method for identifying glycopeptides and analyzing their glycan composition without derivatization of the carbohydrate.

Animals↗

Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707m.

A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33-year-old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low-molecular-weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence-activated cell-sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125-labeled mouse NGF with an affinity of 1.6 x 10(-9) M, and short-term treatment with NGF induces expression by the tumor cells of the proto-oncogene, c-fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor-positive tumor cells. Thus, more than one-third of such tumors might be responsive to the effects of NGF.

Adult↗

Hymenolepis diminuta: the effect of cold temperature exposure on infections in mice.

Hymenolepis diminuta grown in mice maintained at 5 degrees C were significantly larger and markedly more developed than those grown simultaneously in control mice maintained at 21 degrees C. In mice maintained at 5 degrees C, the incidence of infection and the number of worms recovered per host were higher than in the mice kept at 21 degrees C. Regardless of the temperature of the hosts' external environment, primary infections were always expelled before Day 13 postinfection and secondary (challenge) infections were invariably lost before Day 7.

Animals↗

Gallstone ileus masquerading as recurrent carcinoma of the ovary.

A case of gallstone ileus in a patient with carcinoma of the ovary is presented. A 78-year-old female with stage III carcinoma of the ovary underwent optimal debulking surgery followed by six courses of chemotherapy and a microscopically positive second-look laparotomy. She was treated by whole-abdomen pelvic radiation. She then developed progressive nausea, vomiting, abdominal distension, and eventually complete small bowel obstruction. The diagnosis of gallstone ileus was made preoperatively based on the radiological findings. The pathophysiology of gallstone ileus is discussed in the differential diagnosis of patients treated for carcinoma of the ovary.

Aged↗

New analogues of mifepristone with more dissociated antiprogesterone activities.

Mifepristone (RU 486 or RU 38486) possesses strong antiprogesterone and antiglucocorticoid along with moderate antiandrogen properties, which would limit its use in some therapeutic applications. In a search for more dissociated derivatives, the hydroxy substituent and the propynyl group in position 17 of the RU 486 series was replaced by a spiroether group, which is known to induce specific affinity for the progestin receptor in steroid series. The substituents in the para position of the 11 beta-phenyl group, leading to the most potent derivatives in the RU 486 series, were retained. The new derivatives have been studied in vitro for their relative binding affinities (RBAs) for the steroid receptor and in vivo for their hormonal and antihormonal activities. The selected compounds, RU 46556 and RU 49295 display the following properties: in vitro, like RU 486, they show a strong RBA for the rabbit progestin receptor, but a much lower one for the rat thymus glucocorticoid receptor; in vivo they are about three times more active than RU 486 for inducing abortion in rats, but unlike the latter they are devoid of any antiglucocorticoid activity on the thymus weight in rats. These antiprogesterone effects have been confirmed on the deciduoma formation in rats and on the endometrial proliferation in rabbits. However, in contrast to RU 486 in the latter test, some progestomimetic activity has been observed. RU 46556 and RU 49295 are now under extensive pharmacological study.

Abortifacient Agents↗

Long term bone marrow culture in metastatic neuroblastoma.

We have developed a long term marrow culture assay for the study of advanced bone marrow metastatic neuroblastoma. In this in vitro system the hemopoietic growth (GM-CFU) is not affected by the presence of tumor cells. The neuroblastoma cells grow and differentiate partially when in contact with the stromal layer, arresting the culture. We present culture and histological data suggesting that the solid tumors interact specifically with the stromal layer of marrow origin.

Bone Marrow↗

De novo membranous glomerulonephropathy in renal allografts: a report of ten cases and review of the literature.

De novo posttransplantation membranous glomerulonephropathy (MGN) is the most common form of de novo glomerulopathy in renal allografts. The clinical and pathological features of ten patients with de novo MGN were studied and the related literature was reviewed to assess the clinical features, morphologic characteristics, and natural course of this disease. De novo MGN may occur in both living related and cadaveric allografts at any time after transplantation. It presents clinically either as asymptomatic proteinuria or the nephrotic syndrome, a feature of poor prognostic implication. Morphologically, de novo MGN in most instances has distinct differences from idiopathic MGN in native kidneys and is accompanied by varying features of rejection. About 50% of grafts which develop de novo MGN eventually fail. This rather poor outcome may not represent the natural history of de novo MGN per se but rather the consequences of associated chronic rejection. Evidence is presented that many of the cases of so-called de novo MGN may be a complication of transplant glomerulopathy rather than being caused by mechanisms totally independent from rejection.

Cadaver↗

Chromatography of carbohydrates.

The coupling of high-performance anion-exchange chromatography with pulsed amperometric detection provides a much needed analytical tool for the analysis of the carbohydrates of glycoconjugates.

Carbohydrates↗