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Biomedical subjects

P Jordan

Publications and source records attributed to P Jordan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cyclin D1 overexpression lacks prognostic significance in superficial urinary bladder cancer.

The biological behaviour of urinary bladder neoplasms cannot be adequately predicted by histological criteria alone. Cyclin D1 is a cell-cycle regulating protein known to be overexpressed in a proportion of bladder carcinomas. To evaluate the prognostic significance of cyclin D1 expression and its relationship with tumour phenotype, 392 bladder carcinomas were analysed by immunohistochemistry. Clinical follow-up information was available in 337 patients with superficial bladder tumours (stages pTa/pT1). Cyclin D1 positivity was seen in 176 of 392 carcinomas. Cyclin D1 overexpression was strongly linked to papillary tumour growth, low stage, and low histological grade (p<0.005 each). Multivariate analysis showed that papillary tumour growth was the only parameter which was independently linked to cyclin D1 positivity. There was no significant difference in proliferative activity (Ki67 labelling index) between cyclin D1-negative and -positive tumours. Cyclin D1 positivity was not linked to the risk of recurrence or tumour progression, either in pTa or in pT1 carcinomas. It is concluded that cyclin D1 positivity distinguishes a large subgroup of papillary bladder tumours, but there is no evidence of prognostic significance for increased cyclin D1 expression.

Analysis of Variance↗
PubMed1999

A comparison of a new transtelephonic portable spirometer with a laboratory spirometer.

The Spirophone is a new, portable transtelephonic spirometer which records the slow and the forced expiratory vital capacity tests. Data can be transmitted via the telephone to a remote receiving centre, where a volume-time curve and the flow-volume curve are displayed on screen in real time. The aim of this study was to compare the newly developed transtelephonic spirometer, with a laboratory spirometer according to the American Thoracic Society (ATS) testing guidelines. Spirometry indices (slow vital capacity (SVC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), forced expiratory flow at 25, 50 and 75% of FVC (FEF25, FEF50, and FEF75, respectively)) were measured from the SVC and the FVC tests in 45 subjects (30 patients, 15 healthy volunteers) according to the ATS standards. The data obtained with the laboratory system were compared to those from the Spirophone. The Spirophone measurements of SVC, FVC, FEV1, PEF, FEF25, FEF50 and FEF75 correlated closely (r=0.91-0.98) to those from the laboratory system, whereas FEF25, FEF50, and FEF75 were significantly higher with the Spirophone. It is concluded that the Spirophone is comparable to the standard spirometry for home monitoring of slow vital capacity, forced vital capacity, forced expiratory volume in one second and peak expiratory flow. The validity of the manoeuvre can be assessed on screen in real time.

Adult↗
PubMed1999

A correlative morphometric and clinical investigation of hypoganglionosis of the colon in children.

Hypoganglionosis of the myenteric plexus of the colon is not clearly defined and seldom investigated. Colon segments from 15 children with an extended oligoeuronal hypoganglionosis up to the proximal resection end were morphometrically studied and compared to normally innervated colon segments. The study was performed with resected specimens from 7 children with isolated hypoganglionoses, 8 children with a Hirschsprung-associated hypoganglionosis, and 12 colon segments with normal innervation. The resected colon specimens were caudo-cranial coiled. The native tissue was frozen at -80 degrees C on a cryostat carrier and cut at -20 degrees C in 15 microns-thick sections (equivalent to 4-5-micron-thick paraffin sections). The air-dried sections underwent an enzyme-histochemical procedure for an acetylcholinesterase reaction to stain the parasympathetically innervated myenteric plexus. For histological identification and morphometric measurements, ganglia and nerve cells were selectively stained using a lactic dehydrogenase reaction. The morphometric measurements were performed with an optic-electronic image analysis system that determined ganglion size, ganglion distances, nerve cell number per ganglion, and ganglion number per mm colon. The results showed that hypoganglionosis of the myenteric plexus is characterised by a 42% decrease in plexus area and a 55% decrease of the nerve cell number per mm length of colon. The number and area of myenteric ganglia showed a decrease of 59% and a doubling of the ganglion distances. The histopathological diagnosis of a hypoganglionosis of the colon was not necessarily an indication of a chronic constipation, but rather an indication of a disposition for constipation. A chronic constipation is often caused by a long hypoganglionic segment proximal to a resected short Hirschsprung segment.

Cell Count↗
PubMed1999

Hydroxychloroquine overdose: toxicokinetics and management.

BACKGROUND: The management and toxicokinetics of hydroxychloroquine overdose are poorly described. CASE REPORT: We report a case of an 18-year-old girl who ingested 20 g of hydroxychloroquine. She developed marked hypokalemia, hypotension, and ventricular tachyarrhythmias but survived with treatment including intubation, adrenaline infusion, high-dose diazepam, and aggressive potassium replacement. Plasma hydroxychloroquine level was 29.40 mumol/L (9.87 mg/L) 2 hours after ingestion and the elimination half-life of hydroxychloroquine was 22 hours. CONCLUSIONS: The clinical manifestations of this hydroxychloroquine overdose were similar to those reported for chloroquine overdose and the management principles recommended for chloroquine overdose appeared to be efficacious in this case.

Adolescent↗
PubMed1999

Binuclear Drosophila oocytes: consequences and implications for dorsal-ventral patterning in oogenesis and embryogenesis.

The position of the nucleus along the anterior rim of stage 8 Drosophila oocytes presages the dorsal side of the egg and the developing embryo. In this paper, we address the question of whether the oocyte has a previously determined dorsal side to which the nucleus is drawn, or whether nuclear position randomly determines the dorsal side. To do so, we have taken advantage of a genetic system in which Drosophila oocytes occasionally become binuclear. We find that (i) the two nuclei migrate independently to their respective positions on the anterior rim, sometimes selecting the same site, sometimes not, (ii) the two nuclei are equivalent in their ability to induce a dorsal-ventral pattern in the overlying follicular epithelium, and (iii) at any position around the anterior circumference of the egg chamber the follicle cell sheet is equally responsive to the Gurken signal associated with the oocyte nuclei. These results argue that the dorsal-ventral axis is determined arbitrarily by the randomly selected position of the nucleus on the anterior rim of the oocyte. Some of the binuclear eggs support embryonic development. However, despite the duplication of dorsal chorion structures, the majority of such embryos show normal dorsal-ventral patterning. Thus, processes exist in the ventral follicular epithelium or in the perivitelline space that compensate for the expansion of dorsal follicle cell fates and consequently allow the formation of a normal embryonic axis.

Animals↗
PubMed1999

Relative risk of malignant tumors in analgesic abusers. Effects of long-term intake of aspirin.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) e.g. aspirin, indomethacin are reported in epidemiological and experimental studies to reduce the risk for colo-rectal cancer and potentially other malignant tumors. METHODS: We examined the effect of NSAIDs on tumor prevalence in abusers of mixed analgesics containing aspirin, phenacetine, caffeine or codein. 618 analgesic abusers who were autopsied between 1968-1983 were compared with a control group without evidence of analgesic abuse matched for sex, age and year autopsy was performed. RESULTS AND CONCLUSIONS: Abusers were found to have an overall risk of 0.40 fold of having developed a malignancy as compared with the controls. Excluding patients with urinary tract tumors which are increased in analgesic abusers the risk was further decreased to 0.28. No statistically significant effect was found for patients with prostate cancer. The results encourage prospective control studies in high risk patients.

Aged↗
PubMed1998

Cisplatin inhibits synthesis of ribosomal RNA in vivo.

Cis -diammininedichloroplatinum(II) (cisplatin or cis -DDP) is a DNA-damaging agent that is widely used in cancer chemotherapy. Cisplatin crosslinks DNA and the resulting adducts interact with proteins that contain high-mobility-group (HMG) domains, such as UBF(upstream binding factor). UBF is a transcription factor that binds to the promoter of ribosomal RNA (rRNA) genes thereby supporting initiation of transcription by RNA polymerase I. Here we report that cisplatin causes a redistribution of UBF in the nucleolus of human cells, similar to that observed after inhibition of rRNA synthesis. A similar redistribution was observed for the major components of the rRNA transcription machinery, namely TBP, TAFIs and RNA polymerase I. Furthermore, we provide for the first time direct in vivo evidence that cisplatin blocks synthesis of rRNA, while activity of RNA polymerase II continues to be detected throughout the nucleus. The clinically ineffective trans isomer (trans -DDP) does not alter the localization of either UBF or other components of the RNA polymerase I transcription machinery. These results suggest that disruption of rRNA synthesis, which is stimulated in proliferating cells, plays an important role in the clinical success of cisplatin.

Antineoplastic Agents↗
PubMed1998

Coexpression of the HER-2 gene product, p185HER-2, and epidermal growth factor receptor, p170EGF-R, on epithelial ovarian cancers and normal tissues.

Monoclonal antibodies (MAbs) and immunoconjugates reactive with different antigens expressed by neoplastic cells can inhibit tumor growth. Use of these agents in combination with one another or with chemotherapy can exert additive or synergistic cytotoxicity against tumor cells. An augmented therapeutic activity with favorable therapeutic index might be attained when coexpression is observed on tumor cells, but not in normal tissues. In this study frozen sections of 19 ovarian cancers (2 stage I, 10 stage III, 2 stage IV, and 5 recurrent), as well as 29 normal tissues, were evaluated by immunohistochemistry using 11 distinct MAbs against HER-2/p185 and 2 antibodies against EGF-R/p170 to assess coexpression of these receptors. HER-2/p185 expression was detected in 5 to 100% of ovarian cancers and 0 to 50% of normal ovarian epithelia, depending on the antibody used. EGF-R/p170 expression was detected in approximately 70% of cancers and 40% of normal ovaries by both antibodies. Coexpression of p185 and p170 was observed in 47-68% of ovarian cancers and 9-18% of normal ovarian epithelial specimens depending upon the combination of antibodies used. Staining of 273 specimens from 29 normal tissues indicated that coexpression of HER-2 and EGF-R is rare. Normal tissues that coexpressed both receptors in > or =50% of the cases included cervix, endometrium, esophagus, skin, and prostate. These data confirm that HER-2 and EGF-R are more frequently expressed in advanced ovarian cancers than in normal ovarian epithelium and a significant fraction of these tumors coexpress both HER-2 and EGF-R.

Antibodies, Monoclonal↗
PubMed1998

Can academic radiology departments become more efficient and cost less?

PURPOSE: To determine how successful two large academic radiology departments have been in responding to market-driven pressures to reduce costs and improve productivity by downsizing their technical and support staffs while maintaining or increasing volume. MATERIALS AND METHODS: A longitudinal study was performed in which benchmarking techniques were used to assess the changes in cost and productivity of the two departments for 5 years (fiscal years 1992-1996). Cost per relative value unit and relative value units per full-time equivalent employee were tracked. RESULTS: Substantial cost reduction and productivity enhancement were realized as linear improvements in two key metrics, namely, cost per relative value unit (decline of 19.0% [decline of $7.60 on a base year cost of $40.00] to 28.8% [$12.18 of $42.21]; P < or = .001) and relative value unit per full-time equivalent employee (increase of 46.0% [increase of 759.55 units over a base year productivity of 1,651.45 units] to 55.8% [968.28 of 1,733.97 units]; P < .001), during the 5 years of study. CONCLUSION: Academic radiology departments have proved that they can "do more with less" over a sustained period.

Academic Medical Centers↗
PubMed1997

Myosin light chain-activating phosphorylation sites are required for oogenesis in Drosophila.

The Drosophila spaghetti squash (sqh) gene encodes the regulatory myosin light chain (RMLC) of nonmuscle myosin II. Biochemical analysis of vertebrate nonmuscle and smooth muscle myosin II has established that phosphorylation of certain amino acids of the RMLC greatly increases the actin-dependent myosin ATPase and motor activity of myosin in vitro. We have assessed the in vivo importance of these sites, which in Drosophila correspond to serine-21 and threonine-20, by creating a series of transgenes in which these specific amino acids were altered. The phenotypes of the transgenes were examined in an otherwise null mutant background during oocyte development in Drosophila females. Germ line cystoblasts entirely lacking a functional sqh gene show severe defects in proliferation and cytokinesis. The ring canals, cytoplasmic bridges linking the oocyte to the nurse cells in the egg chamber, are abnormal, suggesting a role of myosin II in their establishment or maintenance. In addition, numerous aggregates of myosin heavy chain accumulate in the sqh null cells. Mutant sqh transgene sqh-A20, A21 in which both serine-21 and threonine-20 have been replaced by alanines behaves in most respects identically to the null allele in this system, with the exception that no heavy chain aggregates are found. In contrast, expression of sqh-A21, in which only the primary phosphorylation target serine-21 site is altered, partially restores functionality to germ line myosin II, allowing cystoblast division and oocyte development, albeit with some cytokinesis failure, defects in the rapid cytoplasmic transport from nurse cells to cytoplasm characteristic of late stage oogenesis, and some damaged ring canals. Substituting a glutamate for the serine-21 (mutant sqh-E21) allows oogenesis to be completed with minimal defects, producing eggs that can develop normally to produce fertile adults. Flies expressing sqh-A20, in which only the secondary phosphorylation site is absent, appear to be entirely wild type. Taken together, this genetic evidence argues that phosphorylation at serine-21 is critical to RMLC function in activating myosin II in vivo, but that the function can be partially provided by phosphorylation at threonine-20.

Amino Acid Sequence↗
PubMed1997

DNA aneuploidy, S-phase fraction, nuclear p53 positivity, and survival in non-small-cell lung carcinoma.

Inactivation of the p53 gene plays a key role in tumour biology, probably through a disturbed cell cycle control and an increased genetic instability in p53-inactivated tumours. To learn more about the relationship between p53 alterations, proliferation and genetic instability (DNA aneuploidy) in lung cancer patients, specimens of 220 surgically resected lung carcinomas with clinical follow-up information were examined by immunohistochemistry (p53; CM1) and flow cytometry. Nuclear p53 positivity--found in 49.5% of the tumours--was associated with both high S-phase fraction (SPF) and DNA ploidy aberrations. SPF was higher in p53-positive tumours (15.9 +/- 10.2) than in p53-negative tumours (10.3 +/- 8.7; P = 0.03). The rate of p53 positivity was higher in 101 DNA-aneuploid and DNA-multiploid tumours (55%) than in 27 diploid and peridiploid carcinomas (33%; P = 0.0512). These results are consistent with an in vivo role of p53 inactivation for increased proliferative activity and development of genomic instability in lung cancer. There was no association between SPF and prognosis. Although prognosis was worse in DNA-aneuploid and multiploid tumours than in diploid, peridiploid and tetraploid carcinomas (P = 0.029), DNA ploidy was not an independent predictor of poor prognosis in multivariate analysis. These data show that DNA-flow cytometry has little prognostic value for patients with resected non-small-cell lung carcinoma.

Aneuploidy↗
PubMed1997

The cdk7-cyclin H-MAT1 complex associated with TFIIH is localized in coiled bodies.

TFIIH is a general transcription factor for RNA polymerase II that in addition is involved in DNA excision repair. TFIIH is composed of eight or nine subunits and we show that at least four of them, namely cdk7, cyclin H, MAT1, and p62 are localized in the coiled body, a distinct subnuclear structure that is transcription dependent and highly enriched in small nuclear ribonucleoproteins. Although coiled bodies do not correspond to sites of transcription, in vivo incorporation of bromo-UTP shows that they are surrounded by transcription foci. Immunofluorescence analysis using antibodies directed against the essential repair factors proliferating cell nuclear antigen and XPG did not reveal labeling of the coiled body in either untreated cells or cells irradiated with UV light, arguing that coiled bodies are probably not involved in DNA repair mechanisms. The localization of cyclin H in the coiled body was predominantly detected during the G1 and S-phases of the cell cycle, whereas in G2 coiled bodies were very small or not detected. Finally, both cyclin H and cdk7 did not colocalize with P80 coilin after disruption of the coiled body, indicating that these proteins are specifically targeted to the small nuclear ribonucleoprotein-containing domain.

Carrier Proteins↗
PubMed1997

Modelling of mortality data from a multi-centre study in Japan by means of Poisson regression with error in variables.

BACKGROUND: Death rates of particular categories in epidemiological studies are often based on a small number of occurrences which can be well described by a Poisson distribution. METHOD: We applied this model for the analysis of a multi-centre study in five Japanese counties where the death rates of stomach cancer (ICD-9 code 151) in four age groups are known. In our example some covariates of the cases (e.g. plasma lycopene levels) are unknown values and are estimated from a randomly chosen collective. Therefore these values are subject to a sampling error. The inclusion of errors in variables (e-i-v) into the statistical model can adequately describe such a situation. The model is estimated in a Bayesian framework by means of resampling techniques. RESULTS: Based on the posterior distribution of the parameters the relative risk of stomach cancer is 0.46 (95% confidence interval: 0.23-0.79) comparing the maximum of the population medians of lycopene with the minimum. The estimated overdispersion is close to zero indicating only minor interference with other possible explanatory variables. In addition, we show that inclusion of e-i-v can give more accurate estimates of the parameters even from small sample sizes. CONCLUSIONS: Appropriate statistical methods allow the accurate estimation of relative risks from small sample sizes and from low number of cases. Lycopene plasma levels are good predictors for stomach cancer.

Adult↗
PubMed1997

Carbon dioxide laser as a surgical instrument for sarcoid therapy--a retrospective study on 60 cases.

The objective of this retrospective clinical study was to evaluate the carbon dioxide laser in the treatment of single and multiple sarcoids in 60 animals (44 horses, 13 donkeys, 2 mules, and 1 pony). Only animals that had been operated on 6 mo or more ago were included. Recurrence, new manifestation rate, and cosmetic outcome were determined. Recurrence was observed in 23 (38%) individuals. Animals with new sarcoid manifestation with or without recurrence of a sarcoid were observed in 35 cases (58%). Cases of scar tissue formation and, rarely, leukotrichia were observed. Animals presented with multiple sarcoids were more predisposed to recurrence. Donkeys showed a significantly lower recurrence rate than horses.

Animals↗
PubMed1996

The topography of chromosomes and genes in the nucleus.

At present several lines of evidence indicate that the nucleus is functionally compartmentalized into discrete structures with defined properties. For instance, it is well established that the molecular machines involved in replication, transcription, and RNA processing assemble into morphological entities but it remains unclear whether these correspond to autonomous "organelles" or rather represent temporary accumulations of either active factors recruited onto DNA templates or inactive factors stored in the vicinity of genes. According to the latter view, the spatial distribution of genes during interphase should play a major role in the subnuclear organization of nonchromatin components such as replication, transcription, and processing factors, and in this article we discuss current ideas on the functional compartmentalization of chromosomes and genes within the nucleus.

Binding Sites↗
PubMed1996

Spectroscopic and voltammetric characterisation of the bacterioferritin-associated ferredoxin of Escherichia coli.

The bacterioferritin-associated ferredoxin (Bfd) of Escherichia coli is a 64-residue polypeptide encoded by the bfd gene located upstream of the gene (bfr) encoding the iron-storage haemoprotein, bacterioferritin. The Bfd sequence resembles those of the approximately 60-residue domains found in NifU proteins (required for metallocluster assembly), nitrite reductases, and Klebsiella pneumoniae nitrate reductase. These related-domains contain four well-conserved cysteine residues, which are thought to function as ligands to a [2Fe-2S] cluster. The Bfd protein was over-produced, purified, and characterised. Bfd was found to be a positively-charged monomer containing two iron atoms and two labile sulphides. Ultraviolet-visible, EPR, variable-temperature magnetic-circular dichroism and resonance Raman spectroscopies, together with cyclic voltogram measurements, revealed the presence of a [2Fe-2S]2+,+ centre (E1/2 = -254 mV) having remarkably similar properties to the Fe-S cluster of NifU. Bfd may thus be a 2Fe ferredoxin participating either in release/delivery of iron from/to bacterioferritin (or other iron complexes), or in iron-dependent regulation of bfr expression.

Amino Acid Sequence↗