Biomedical subjects

N A Cross

Publications and source records attributed to N A Cross.

9 recordsLinked to original sources

PubMed2006

Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma.

PURPOSE: Loss of chromosome 3 is a frequent event in uveal melanomas, which is associated with hepatic metastases and a poor prognosis. The entire copy of chromosome 3 is usually lost (monosomy 3); however, a small subset of tumours demonstrate partial deletions of chromosome 3. Analysis of these tumours may allow the identification of tumour suppressor genes (TSGs) that are the molecular target of monosomy 3. Therefore, the purpose of this investigation was to determine the location of these partial deletions of chromosome 3 in uveal melanomas. METHODS: Microsatellite analysis and restriction fragment-length polymorphism analysis were performed on 52 primary uveal melanomas using 19 markers located on both arms of chromosome 3. Cytogenetic analysis and fluorescence in situ hybridisation were performed, where possible, to confirm molecular findings. RESULTS: Of 52 tumours studied, five tumours (10%) demonstrated LOH at one or more informative markers, but retention of heterozygosity was observed at other loci on chromosome 3, consistent with the presence of structural abnormalities to chromosome 3. Consistent with previous findings, the pattern of LOH in these tumours indicates the presence of deletions around 3p25-26 and on 3q, and that a new target region at 3p11-14 is preferentially deleted. CONCLUSIONS: These results indicate the presence of several tumour suppressor loci on chromosome 3 and support the notion that the high rate of monosomy 3 in uveal melanoma is driven by disruption of several TSGs located on both arms of chromosome 3.

Chromosome Deletion↗

PubMed2005

The expression and regulation of ADAMTS-1, -4, -5, -9, and -15, and TIMP-3 by TGFbeta1 in prostate cells: relevance to the accumulation of versican.

BACKGROUND: Benign prostatic hyperplasia (BPH) is characterized by a proportional increase in the size of the stromal compartment of the gland, involving alterations to extracellular matrix (ECM) components. Some of these changes have been associated with the activity and expression of transforming growth factor beta1 (TGFbeta1). Versican (chondroitin sulphate proteoglycan-2) is overexpressed in BPH and prostate cancer and potentially contributes to disease pathology. A sub-group of the ADAMTS lineage of metalloproteases possess versican-degrading properties and are potential regulators of proteoglycan accumulation associated with BPH. These enzymes have one major inhibitor in the ECM, tissue inhibitor of metalloproteinases (TIMP)-3. METHODS: The effect of TGFbeta on mRNA expression in prostatic stromal cells was determined by real-time qRT-PCR using primers to ADAMTS-1, -4, -5, -9, -15, versican, and TIMP-3. MMP-inhibitory potential (TIMP activity) of conditioned medium was measured using a fluorometric peptide substrate. RESULTS: Prostatic stromal cell cultures consistently expressed ADAMTS-1, -4, -5, -9, -15 and TIMP-3, in contrast to PC3, DU145, and LNCaP cells which failed to express at least two ADAMTS transcripts. In stromal cells, TGFbeta1 decreased ADAMTS-1, -5, -9, and -15 transcripts and increased ADAMTS-4, versican, and TIMP-3. TGFbeta also increased TIMP activity in conditioned medium. CONCLUSIONS: The induction of versican expression by TGFbeta in BPH stromal cells is in agreement with histological studies. The negative effect of TGFbeta1 on ADAMTS-1, -5, -9, and -15 coupled with increases in their inhibitor, TIMP-3 may aid the accumulation of versican in the stromal compartment of the prostate in BPH and prostate cancer.

ADAM Proteins↗

PubMed2004

Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast cancer cells from TRAIL-induced apoptosis.

Advanced breast cancer is often associated with metastatic bone disease, causing a number of serious complications for the patients such as hypercalceamia, pain, nerve compression and fractures. The formation of bone metastases depends on complex interactions between tumour cells and the cells of the bone microenvironment, but the precise molecular mechanisms involved in the development of tumour-induced bone disease have not been identified. We have investigated the ability of bone marrow stromal cells (BMSC) isolated from breast cancer patients to generate osteoprotegerin (OPG), a molecule involved both in bone turnover and cell survival. The potential survival effects of OPG are mediated through binding to a member of the TNF super family, TNF-related Apoptosis Inducing Ligand (TRAIL), preventing association between TRAIL and its death-inducing receptors present on a number of tumour cell types. In the present report we show that bone marrow stromal cells isolated from breast cancer patients produce OPG when grown in culture. The levels of OPG present in BMSC conditioned medium is sufficient to protect breast cancer cells from undergoing TRAIL induced apoptosis. Our data suggest that bone-derived OPG may increase survival of breast cancer cells that reach the bone microenvironment as part of the metastatic process.

Apoptosis↗

PubMed1999

Antimicrobial susceptibility testing of Chlamydia trachomatis using a reverse transcriptase PCR-based method.

The conventional method for antimicrobial susceptibility testing of Chlamydia trachomatis is subjective and potentially misleading. We have developed a reverse transcriptase PCR (RT-PCR)-based method which is more sensitive and less subjective than the conventional method. Using 16 strains of C. trachomatis in triplicate assays, we found the RT-PCR method consistently more sensitive than the conventional technique for all eight antimicrobials tested, with resultant MICs determined by RT-PCR ranging from 1.6-fold higher (erythromycin) to >/=195-fold higher (amoxicillin).

Amoxicillin↗

PubMed1998

The effects of calcium supplementation, duration of lactation, and time of day on concentrations of parathyroid hormone-related protein in human milk: a pilot study.

This pilot study reports parathyroid hormone-related protein (PTHrP) in milk from 14 women (placebo = 6, calcium = 8) over the duration of lactation. Milk samples collected 0 to 250 days postpartum were assayed for PTHrP by a two-site immunoradiometric assay. PTHrP concentrations were significantly lower in colostrum 0-4 days postpartum (5,080 +/- 1575 pmol/L) than at 7-60 days postpartum (11,863 +/- 1528-14,213 +/- 1574 pmol/L); concentrations did not differ between calcium and placebo groups. A suggestive diurnal variation was seen in two women who collected milk samples over 48 continuous hours. Confounding factors related to milk synthesis and milk sampling contribute to variability in PTHrP concentrations.

Adult↗

PubMed1995

Changes in bone mineral density and markers of bone remodeling during lactation and postweaning in women consuming high amounts of calcium.

A randomized clinical intervention trial to determine effects of lactation and 1 g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7, placebo [P] = 8) consuming 1.3-2.4 g of Ca/day from diet + prenatal supplement. Study periods were baseline, < or = 2 weeks postpartum; lactation, 3 months lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD) corrected for body weight was determined by dual-energy X-ray absorptiometry (DXA). Indicators of calcium metabolism, bone turnover, and lactation were measured: calcium metabolism, parathyroid hormone (PTH), 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D); bone turnover, formation, procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase (B-ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation, prolactin (PRL). Mean BMD changes differed by site: baseline to lactation -4.3% (P) (p < 0.04) and -6.3% (Ca) (p < 0.01) at the lumbar spine (L2-L4) and 5.7% gains of the ultradistal (UD) radius (Ca) (p < 0.04); lactation to postweaning, -6% to -11% at all sites of the radius and ulna (Ca, P) (p < 0.04) +3% at L2-L4 (Ca) (p < 0.03); baseline to postweaning, (UD) radius -5.2% (P) (p < 0.03), UD radius + ulna -6% to -8% (Ca, P) (p < 0.04) but no significant loss of L2-L4 or total body. Bone turnover markers were higher at lactation than postweaning: PICP (+34%, p < 0.001), osteocalcin (+25%, p < 0.01), TRAP (+11%, p < 0.005) as well as PRL (+81%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study.

Ten women were followed serially to determine the effect of stages of reproduction on calcium and bone metabolism. The study periods were nonpregnant nonlactating, the end of each trimester of gestation, 3 mo lactation, and postweaning. Comparisons were with nonpregnant nonlactating status for each individual. Fractional calcium absorption (P < 0.0001) and concentrations of 1,25-dihydroxyvitamin D (P < 0.01) were higher in the second and third trimesters. Total urinary calcium was higher during pregnancy and lower postweaning. Parathyroid hormone (PTH) concentrations were higher only postweaning (P < 0.01). Markers of bone turnover increased at the third trimester and during lactation: serum tartrate resistant acid phosphatase and bone specific alkaline phosphatase, and urinary deoxypyridinoline (P < 0.01). Serum procollagen I carboxypeptides increased only in the third trimester (P < 0.01). Bone mineral density by single-photon absorptiometry did not differ by period. We conclude that absorption and urinary excretion of calcium increase during pregnancy whereas bone turnover increases during late pregnancy and lactation; only renal changes consistent with an increase in PTH were seen postweaning.

Absorption↗

PubMed1982

Subcortical structures projecting to visual cortical areas in squirrel monkey.

In 17 adult squirrel monkeys (Saimiri), horseradish peroxidase was used as a retrograde tracer substance to reveal the subcortical structures (other than the lateral geniculate nucleus and pulvinar) which project to the occipital lobe, and, in particular, to the central visual field representation in areas, 17, 18, 19, and MT. Evidence is provided that each of areas 17, 18, and MT receives a projection from locus coeruleus, nucleus dorsalis raphae, nucleus annularis, nucleus centralis superior, formation reticularis pontis oralis, nucleus basalis of Meynert, lateral hypothalamus, claustrum, and nuclei paracentralis and centralis medialis thalami. Area 19 receives a projection from all these structures except from the nucleus annularis. Only area MT was determined to be a target of a projection from the nucleus linearis. For technical reasons, only area MT was determined to receive afferent fibers from the nucleus basalis lateralis amygdalae. The results indicate that there is no topographical organization of subcortical inputs to the central visual field representation in individual cortical areas.

Animals↗

PubMed1981

Areal and laminar distribution of neurons interconnecting the central visual cortical areas 17, 18, 19, and MT in squirrel monkey (Saimiri).

The retrogradely transported horseradish peroxidase (HRP) method was used to study the areal and laminar distribution of neurons sending their axons to ipsilateral and contralateral visual cortical areas 17, 18, 19, and MT in the squirrel monkey. Further details regarding neuron type (stellate or pyramidal), size class, and spatial grouping of the cells making these corticocortical connections also were obtained. All interareal connections are reciprocal. Ipsilaterally, such connections exist between areas 17 and 18, 17 and MT, 18 and 19, 18 and MT, and 19 and MT. In addition, areas 18, 19, and MT receive association fibers from the ipsilateral frontal eye field; when combined with previous findings, these results indicate the existence of reciprocal connections between area 18 and the frontal eye field and between area MT and the frontal eye field. Each of areas 18, 19, and MT. Area 17 has only weak callosal connections. Both the ipsilateral and the contralateral connections are topographically organized such that they obey a hodological principle of visuotopic connectivity: that is, only representations of the same part of the visual field are interconnected. With regard to layers of origin, the callosal neurons of these visual areas conform to the general concept of corticocortical fibers arising from supragranular layers in that most of them are located in layer IIIb; only a few of them reside at the junction between layers V and VI. On the other hand, for all the visuocortical connections investigated, the anteriormost area of a reciprocally interconnected pair has its association neurons located predominantly in the infragranular layers while the posteriormost area has its association neurons located primarily in layer III. All callosal fibers and most association fibers arise from pyramidal cells. The callosal cells are larger and reside at a deeper level in layer III than neurons with ipsilateral corticocortical connections. However, some of the association cells at the junction of layers V and VI in area 17 which project to area MT are relatively large and may include the solitary cells of Meynert; but medium-sized pyramidal cells also participate in this projection. In area 17, some association neurons in layers IIIb and IIIc which project to area 18, as well as some in layer IIIc which project to area MT, are most likely stellate cells. Several different patterns of cell groupings were observed for the central representation interconnections. Neither ipsilateral area MT nor any of the contralateral visuocortical areas had multiple groupings of labeled neurons. The ipsilateral projections from area 17 to 18, 17 to MT, and 18 to 19 were arranged similarly according to a plan involving separate, multiple loci of origin for cells projecting to a small and isolated subregion of the central representation in the target cortical area; following larger injections, cells throughout the central representation of the projecting cortex were labeled...

Animals↗