Familial male breast cancer.
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Breast Neoplasms, Male↗
Biomedical subjects
C Jones
Publications and source records attributed to C Jones.
Fumonisins and Alternaria alternata lycopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells.
Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL) toxins are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain. These mycotoxins represent a serious threat to human and animal health, inducing both cell death and neoplastic events in mammals. The mechanisms by which this family of chemical congeners induce changes in cell homeostasis were investigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative components of signal transduction pathways involved in apoptosis. Structurally, these mycotoxins resemble the sphingoid bases, sphingosine and sphinganine, that are reported to play critical roles in cell communication and signal transduction. The addition of fumonisin B1 or AAL toxin, TA, to CV-1 cells induced the stereotypical hallmarks of apoptosis, including the formation of DNA ladders, compaction of nuclear DNA, and the subsequent appearance of apoptotic bodies. Neither mycotoxin induced cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressing simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B1 induced cell cycle arrest in the G1 phase in CV-1 cells but not in COS-7 cells. AAL toxin TA did not arrest cell cycle progression in either cell line. The induction of apoptosis combined with the widespread presence of these compounds in food crops and animal feed identifies a previously unrecognized health risk to humans and livestock. These molecules also represent a new class of natural toxicants that can be used as model compounds to further characterize the molecular and biochemical pathways leading to apoptosis.
Alternaria↗
The cAMP receptor subtype cAR2 is restricted to a subset of prestalk cells during Dictyostelium development and displays unexpected DIF-1 responsiveness.
Dictyostelium discoidium cells express a family of cell surface cAMP receptors, and these G-protein-coupled receptors are each expressed with unique spatial and temporal patterns. One of these receptors, cAR2, is present during the postaggregative stages of development and our previous work suggests that it is preferentially expressed in prestalk cells. We report here the isolation of the promoter for carB, the gene which encodes cAR2. Using this fragment to generate a carB::lacZ, gene fusion construct, we investigated carB expression in detail. Expression is first detected at the tight aggregate stage and subsequently in a pattern reminiscent of the prestalk-specific gene ecmA. There are subtle differences, however, with, ecmA being expressed significantly in the anterior-like cells of the migrating pseudoplasmodium and in the basal disc and lower cup supporting the sorus during terminal development. carB is not expressed in any of these places. The presence of these different prestalk cell subtypes was confirmed by double indirect immunofluorescence using anti-cAR2 and anti-beta-galactosidase antibodies. While virtually all cAR2-expressing cells also express ecmA::lacZ, a substantial fraction of ecmA::lacZ-positive cells do not express cAR2. We also found the regulation of carB gene expression to differ from that of ecmA. carB expression is induced in vitro by extracellular cAMP, but surprisingly, not by DIF-1, a soluble molecule thought to be essential for the initiation of prestalk differentiation. Thus, cAR2 appears to be a cAMP receptor present on a restricted subset of prestalk cells and whose expression does not respond typically to the prestalk inducer DIF-1. DIF-1 sensitivity may, therefore, not be characteristic of all early prestalk differentiation.
Amino Acid Sequence↗
Early and periodic screening diagnosis and treatment.
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Attitude of Health Personnel↗
Trisomy 12/monosomy X/normal female mosaicism: prenatal detection and confirmation in a liveborn.
We report a case of mosaicism for three cell lines: 45,X, 46,XX, and 47,XX, + 12, diagnosed prenatally by amniocentesis done for advanced maternal age. Cord blood from the baby showed mosaicism for 45,X and 46,XX; cultures derived from multiple placental sites, villi, cord, membrane, and skin had varying proportions of all three cell lines. The patient at 18 months of age has mild physical dysmorphisms, hypotonia, delay in gross motor development, and age-appropriate cognitive development. The literature reveals variable outcomes for individuals with either mosaic trisomy 12 or mosaic Turner syndrome. Parental origin of the chromosome involved in a proposed corrected trisomy and/or the percentage of cell types in affected organs might account for the variability in outcomes seen.
Adult↗
Cross-cultural differences in maternal evaluation of children's body shapes.
OBJECTIVE: This study investigated cultural variation in mothers' attitudes to children's body shape. METHOD: One hundred thirty-one mothers from five cultural groups attending a pediatric clinic were approached, and data obtained from 114. Background information was obtained, including weight and height for themselves and their children. Mothers completed the Eating Attitudes Test (EAT-26) and rated drawings of children for attractiveness and health, using Likert scales, scored 1-7. RESULTS: Mothers from the different cultural groups had similar body mass index (BMI) and EAT scores, and their children had similar average body weight. However, UK mothers found slimmer girls attractive compared to mothers from South Asia, the Mediterranean or the Caribbean regions, and sub-Saharan Africa (p < .05). The differences occurred within the mid-range (median scores for all ethnic groups 4-5). South Asian mothers presented to the pediatric clinic with more worries about their children not gaining weight and growth (p < .01). DISCUSSION: These findings have implications for understanding cultural variation in the acquisition of attitudes to body shape, and these attitudes influence medical help seeking.
Attitude↗
Chemistry and biological activity of AAL toxins.
AAL toxins and fumonisins comprise a family of highly reactive, chemically related mycotoxins that disrupt cellular homeostasis in both plant and animal tissues. Two critical issues to resolve are the detection of the entire family in food matricies and the mode of cellular disruption. Analysis of the entire set of chemical congeners in food matrices is difficult but has been achieved by a combination of different HPLC and mass spectrometry strategies. The mode of cellular disruption is unknown but likely involves changes associated with the inhibition of ceramide synthase in both plants and animals. Toxin treated cells exhibit morphological and biochemical changes characteristic of apoptosis. Further evaluation of the specific genetic and biochemical changes that occur during toxin-induced cell death may aid in understanding the mole of the action of these mycotoxins.
Alternaria↗
Structural variation in the glycoinositolphospholipids of different strains of Trypanosoma cruzi.
The structures of the glycoinositolphospholipids (GIPLs) from five strains of the protozoan parasite Trypanosoma cruzi have been determined. Two series of structures were identified, all but one containing the same Man4(AEP)GlcN-Ins-PO4 core. Series 1 oligosaccharides are substituted at the third mannose distal to inositol (Man 3) by ethanolamine-phosphate or 2-aminoethylphosphonic acid, as are some glycosyl-phosphatidylinositol-protein anchors of T. cruzi. The core can be further substituted by terminal (1-3)-linked beta-galactofuranose units. In contrast, Series 2 oligosaccharides do not have additional phosphorus-containing groups attached to Man 3, the latter being substituted instead by a single side chain unit of beta-galactofuranose. Series 1 oligosaccharides are present in all strains (G, G-645, Tulahuen CL, and Y) whereas Series 2 structures are present mainly in CL and Y strains. The lipid moiety in the GIPLs from the G, G-645 and Tulahuen strains is predominantly ceramide, as reported for the Y strain, whilst that from the CL strain is a mixture of ceramide and alkylacylglycerol species. The lipid moiety of the GIPLs, and probably also the phosphoinositol-oligosaccharide structures may play an important immunomodulatory role in infection by T. cruzi.
Aminoethylphosphonic Acid↗
The chromosomal distribution and organization of sheep satellite I and II centromeric DNA using characterized sheep-hamster somatic cell hybrids.
A panel of sheep-hamster somatic cell hybrids containing single sheep chromosomes was used to study the chromosomal distribution and organization of two families of sheep centromeric satellite DNA. This study shows that the centromeres of the sheep metacentric chromosomes 1, 2 and 3 differ in their organization and relative quantities of sheep satellite I DNA. The results, when correlated with the proposed formation of these metacentric chromosomes by ancient Robertsonian translocations, suggest a loss or replacement of satellite I centromeric DNA from the centromeres of these sheep chromosomes. Using Southern blot analysis and fluorescence in situ hybridization, this study shows that the recent centric fusion chromosome t2 (rob 9;10) contains little satellite II DNA. Together these results suggest the possibility of substantial reorganization of sheep centromeric DNA families after Robertsonian translocations.
Animals↗
EagI and NotI linking clones from human chromosomes 11 and Xp.
EagI and NotI linking libraries were prepared in the lambda vector, EMBL5, from the mouse-human somatic cell hybrid 1W1LA4.9, which contains human chromosomes 11 and Xp as the only human component. Individual clones containing human DNA were isolated by their ability to hybridise with total human DNA and digested with SalI and EcoRI to identify the human insert size and single-copy fragments. The mean (+/- SD) insert sizes of the EagI and NotI clones were 18.3 +/- 3.2 kb and 16.6 +/- 3.6 kb, respectively. Regional localisation of 66 clones (52 EagI, 14 NotI) was achieved using a panel of 20 somatic cell hybrids that contained different overlapping deletions of chromosomes 11 or Xp. Thirty-nine clones (36 EagI, 3 NotI) were localised to chromosome 11; 17 of these were clustered in 11q13 and another nine were clustered in 11q14-q23.1. Twenty-seven clones (16 EagI, 11 NotI) were localised to Xp and 10 of these were clustered in Xp11. The 66 clones were assessed for seven different microsatellite repetitive sequences; restriction fragment length polymorphisms for five clones from 11q13 were also identified. These EagI and NotI clones, which supplement those previously mapped to chromosome 11 and Xp, should facilitate the generation of more detailed maps and the identification of genes that are associated with CpG-rich islands.
Animals↗
Familial amyotrophic lateral sclerosis with a mutation in exon 4 of the Cu/Zn superoxide dismutase gene: pathological and immunocytochemical changes.
Detailed molecular pathology studies and clinicopathological phenotyping of familial amyotrophic lateral sclerosis (FALS) with characterised mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) will yield important insights into the pathogenesis of motor neuron degeneration. An autopsy case is described with the mutation E100G (exon 4) of the SOD1 gene in which full neuropathological examination including immunocytochemistry of ubiquitin and neurofilament epitopes was performed. The case falls into the category of "amyotrophic lateral sclerosis (ALS) with posterior column involvement." Critical analysis of the findings indicates a truly multisystem disorder in which ascending sensory pathways and components of the efferent cerebellar pathways are at least as severely affected as the motor system. Abnormal neurofilament phosphorylation was not a prominent feature. Ubiquitinated neuronal inclusions were infrequent except in the hippocampal denate granule cells where they were indistinguishable from sporadic cases of ALS-dementia. The motor cortex was preserved despite severe distal axonal loss in the corticospinal tract. These findings suggest a primary failure of axonal maintainance affecting several neuronal groups with long projecting axons. The differences and similarities compared to previously reported case with I113T (exon 4) and A4T (exon 1) mutations are discussed. Findings related to inflammatory cell infiltration, ubiquitination and neurofilament phosphorylation are discussed with reference to the pathogenesis of sporadic ALS.
Adult↗
Conservative management of placenta percreta with involvement of the ileum.
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Adult↗
Source of respiratory drive during periodic breathing in lambs.
In order to investigate the mechanisms underlying periodic breathing (PB), we studied the initiation of breathing after passive hyperventilation in 14 anaesthetised 10-20 day old lambs. Eight of the lambs exhibited PB following post-hyperventilation apnea (PHA), with an epoch duration of 82.4 +/- 14.2 sec (mean +/- SEM), a cycle duration of 9.7 +/- 0.7 sec and a ratio of ventilatory duration to apnea duration (V-A ratio) of 1.24 +/- 0.32. The remaining lambs showed stable breathing patterns following PHA. The ventilatory response to isocapnic hypoxia was significantly greater in the group that had PB (-7.2 +/- 1.0 ml min-1% Sao2-1 kg-1) than in the animals that did not (-2.5 +/- 1.0 ml min-1%Sao2-1 kg-1). Using experimentally determined ventilatory response curves to O2 and CO2 we calculated that the swings in Sao2 and Paco2 during PB generated chemical drive that accounted for only 16.2% of the ventilatory oscillations observed during PB. Much of the remaining drive appeared to originate in the 'switch-on' characteristics of the respiratory controller, in lambs that exhibited periodic breathing, when breathing began after PHA ventilation jumped abruptly from zero to 55.1% of the eupneic ventilation. The magnitude of this jump in ventilation accounted for 51.9% of the amplitude of ventilatory oscillations that occur during PB. We speculate that this previously unrecognised feature of the respiratory controller, together with an elevated sensitivity to hypoxaemia, play crucial roles in generating PB in the infant.
Animals↗
Insulin resistance in patients with essential hypertension can occur in the absence of microalbuminuria.
This study was initiated to see if the presence of resistance to insulin-mediated glucose disposal, glucose intolerance, and hyperinsulinemia in healthy patients with hypertension was dependent upon the coexistence of microalbuminuria. For this purpose we compared these variables in 68 individuals: 34 patients with hypertension and 34 normal volunteers. The two groups were similar in terms of age, gender distribution, body mass index, and ratio of waist to hip girth. Furthermore, although four patients with hypertension satisfied the criteria for microalbuminuria, as compared to one normal volunteer, the urinary albumin excretion (UAE) rates were similar in the two groups (8.07 +/- 1.08 v 7.67 +/- 1.12 micrograms/min). Despite the similarities, both the plasma glucose and insulin responses to a 75 g oral glucose challenge were significantly higher (P < .01) in those with high blood pressure. In addition, the steady-state plasma glucose (SSPG) concentrations at the end of a 180 min continuous infusion of somatostatin, insulin, and glucose was significantly higher in those with hypertension (156 +/- 13 v 107 +/- 10 mg/dL, P < .01). Since the steady-state plasma insulin levels were also somewhat higher in those with hypertension, the higher SSPG values indicate that these individuals were relatively insulin resistant as compared to the control population. Finally, UAE rates were not correlated with either the plasma glucose or insulin responses to oral glucose or to the SSPG concentrations--either in the entire group of 68, or when the 34 patients in each group were considered separately. These results demonstrate that insulin resistance, glucose intolerance, and hyperinsulinemia can occur independently of microalbuminuria in patients with hypertension.
Albuminuria↗
Physicochemical and immunological studies on the stability of free and microsphere-encapsulated tetanus toxoid in vitro.
The stability of tetanus toxoid released from experimental, slow-release microsphere vaccines was compared with that of free toxoid under different conditions over a 3 month period. The amount of antigenicity remaining, as measured by ELISA, correlated well with loss of toxoid structure, as determined by circular dichroism and fluorescence spectroscopy. At 37 degrees C and low pH, pH 2.5 for free toxoid, or under the acidic conditions generated by the hydrolysis of fast-release microspheres, a gradual unfolding of the polypeptide chain was observed within the first few weeks with more rapid denaturation beyond 30 days.
Drug Stability↗
The D2 receptor occupancy profile of loxapine determined using PET.
Positron emission tomography (PET) studies of typical neuroleptics suggest that 60% to 80% of striatal D2 occupancy may be sufficient for optimal clinical treatment of psychosis. Therefore, striatal D2 occupancy may be used as an index to determine the optimal dose range. Toward this end, we determined the in vivo D2 profile of loxapine, using [11C]-raclopride and PET. Seven patients selected from a clinical population were scanned while taking steady-state oral loxapine from 10 to 100 mg/day. Their D2 receptor occupancy was estimated by comparing them to age-matched data from neuroleptic-naive patients. The D2 receptor occupancy ranged from 52% to 90%, and there was a very strong relationship between dose and D2 occupancy, suggesting that 15 to 30 mg/day of loxapine would produce, the putatively optimal, 60% to 80% striatal D2 blockade. This dose range is much lower than that used in most clinical settings and points to the potential efficacy of loxapine at lower doses.
Administration, Oral↗
Effect of parenteral L-glutamine on muscle in the very severely ill.
Glutamine (Gln)-supplemented perioperative total parenteral nutrition (TPN) has been reported to reduce the loss of intramuscular glutamine following routine surgery. This study investigates whether glutamine-supplemented TPN can alter muscle biochemistry acutely in the very severely ill patient. Thirty-eight patients (age 19-77 yr; mean 55 yr), critically ill (APACHE II range 8-31; median 17) admitted to the intensive care unit (ICU) were recruited to receive either conventional TPN (CTPN) or an isonitrogenous, isoenergetic feed supplemented with 25 g crystalline L-glutamine per 24 h (GTPN) in a prospective, double blind, block-randomized study. In a representative sample of these patients, relatives consented to a paired muscle biopsy taken before feeding (10 GTPN/9 CTPN patients; ICU Day 2-4) and repeated 5 days later (16 patients; ICU Day 7-9). Muscle biopsies and matching plasma samples were analyzed using a coupled glutaminase-glutamate dehydrogenase enzymatic assay. A correction was made using sodium to account for the massive changes in extracellular fluid volume. The average muscle Gln content before feeding was very low. Between biopsies no consistent pattern of change was seen with or without exogenous Gln. It also proved difficult in these very sick patients to correct a low plasma Gln with L-Gln-TPN during the initial phase of the severe illness. TPN supplementation with 25 g/24 h, L-glutamine appears inadequate in the acute period to counteract the muscle and plasma biochemical changes seen in these patients. It is unknown whether any larger dose could alter this state.
Adult↗
Genetic dissection of memory in Drosophila.
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Animals↗