Biomedical subjects

P Jordan

Publications and source records attributed to P Jordan.

At least 73 records · Page 4Linked to original sources

PubMed1996

Reconstitution of the [4Fe-4S] cluster in FNR and demonstration of the aerobic-anaerobic transcription switch in vitro.

The FNR protein of Escherichia coli is a redox-responsive transcription regulator that activates and represses a family of genes required for anaerobic and aerobic metabolism. Reconstitution of wild-type FNR by anaerobic treatment with ferrous ions, cysteine and the NifS protein of Azotobacter vinelandii leads to the incorporation of two [4Fe-4S]2+ clusters per FNR dimer. The UV-visible spectrum of reconstituted FNR has a broad absorbance at 420 nm. The clusters are EPR silent under anaerobic conditions but are degraded to [3Fe-4S]+ by limited oxidation with air, and completely lost on prolonged air exposure. The association of FNR with the iron-sulphur clusters is confirmed by CD spectroscopy. Incorporation of the [4Fe-4S]2+ clusters increases site-specific DNA binding about 7-fold compared with apo-FNR. Anaerobic transcription activation and repression in vitro likewise depends on the presence of the iron-sulphur cluster, and its inactivation under aerobic conditions provides a demonstration in vitro of the FNR-mediated aerobic-anaerobic transcriptional switch.

Aerobiosis↗

PubMed1996

Genetic aberrations detected by comparative genomic hybridization are associated with clinical outcome in renal cell carcinoma.

The clinical behavior of renal cell carcinoma (RCC) cannot be predicted by histological and other markers. In this study, comparative genomic hybridization was used to evaluate whether the number of genomic aberrations has prognostic significance in 41 nonmetastatic clear cell RCC extending beyond the renal capsule. Losses were most prevalent at 3p (56%) and 9p and 13q (24% each). The number of DNA losses per tumor was associated with recurrence-free survival (P = 0.03). DNA gains most often involved chromosome 5q (17%) and chromosome 7 (15%). The number of DNA gains was not associated with clinical outcome. Loss of chromosome 9p was the only individual locus associated with recurrence (P = 0.04), suggesting that a tumor suppressor gene on chromosome 9p may play a role in RCC progression.

Carcinoma, Renal Cell↗

PubMed1996

Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma.

The prognosis of operated patients with non-small cell lung cancer (NSCLC) is poor despite thorough pre-operative staging. An improved preselection is needed of patients likely to profit from surgery. This study was undertaken to evaluate the prognostic significance of nuclear p53 overexpression in a cohort of 247 surgically treated patients with NSCLC. It showed that the prevalence of immunohistochemically detectable p53 overexpression varied between different tumour types. p53 overexpression was equally frequent in large cell carcinoma (53 per cent) and in squamous cell carcinoma (54 per cent), but significantly less frequent in adenocarcinoma (34 per cent; P = 0.009). p53 overexpression was particularly rare in bronchioloalveolar carcinoma (positivity in 1 of 17 cases). These variations may reflect aetiological differences between the histological subtypes. p53 overexpression was also associated with high tumour grade (P = 0.0157) and the presence of lymph node metastasis (P = 0.0259), but not with advanced tumour stage. Survival analysis showed no difference in clinical outcome between p53-positive and p53-negative tumours within 101 node-positive tumours. In contrast, survival time was significantly better in p53-negative tumours than in p53-positive tumours within the group of 113 node-negative tumours (P = 0.032). Stepwise regression analysis showed that p53 overexpression is an independent prognostic factor in node-negative NSCLC.

Biomarkers, Tumor↗

PubMed1996

Ki67 labelling index: an independent predictor of progression in prostate cancer treated by radical prostatectomy.

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. Both tumour cell proliferation and neuroendocrine differentiation have been suggested as additional prognostic parameters, neuroendocrine differentiation being considered to enhance tumour cell proliferation. This study investigated the prognostic value of tumour cell proliferation [Ki67 labelling index (LI), MIB 1] and neuroendocrine differentiation and their relationship to each other. One hundred and thirty-seven paraffin-embedded radical prostatectomy specimens were examined. Neuroendocrine differentiation was found in 58 per cent of cases, but was not associated with pTN stage, Gleason score, Ki67 LI, or tumour progression. Ki67 LI was not significantly associated with pTN stage or with Gleason score. High grade (P = 0.0005), advanced local stage (P = 0.0004), positive lymph nodes (P = 0.02), and high Ki67 LI (P = 0.0203) were predictors of tumour progression if univariate analysis was performed, but Cox stepwise regression showed that only advanced local stage (P = 0.0025) and Ki67 LI (P = 0.0105) were independent predictors of tumour progression, the relative risk being 3.6 and 2.5, respectively. It is concluded that Ki67 is an important prognostic marker in prostate cancer with a potential for routine application.

Aged↗

PubMed1996

Utility of the Pediatric Symptom Checklist as a psychosocial screen to meet the federal Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards: a pilot study.

OBJECTIVE: To examine the usefulness of the Pediatric Symptom Checklist (PSC) as the psychosocial screening measure to meet federal Medicaid/Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards in a low-income Hispanic community. DESIGN AND SETTING: Three hundred seventy-nine children (aged 6 to 16 years) were screened with the PSC in a 10-month period during well child visits to three clinics in Ventura and San Mateo counties in California. The PSC was available in English and Spanish and was administered both in written (paper-and-pencil) and oral formats. Follow-up services were provided for children identified as needing evaluation. RESULTS: The Cronbach alpha was high (r = 0.91) for the PSC in the whole sample and virtually identical for English, Spanish, oral, and written formats. All the PSC items were significantly associated with total score on the PSC in English, Spanish, oral, and written formats. Overall, the PSC identified 10.6% of the sample as at risk for psychosocial problems. Thirty-six children (9.5% of sample) were referred for mental health follow-up. Public health data from Ventura County showed a statistically significant increase in referrals for psychologic problems during the study period in two locations using the PSC: from 0.5% to 2.9% of the school-aged children seen. CONCLUSION: The PSC provides a feasible, well-accepted method for screening for psychosocial problems during EPSDT examinations of school-aged children. Psychosocial screening using a validated instrument such as the PSC, as well as increased efforts to refer positive screening results, track outcomes, and assess cost benefits should be essential requirements in capitated Medicaid approaches to caring for poor children.

Adolescent↗

PubMed1996

In vivo evidence that TATA-binding protein/SL1 colocalizes with UBF and RNA polymerase I when rRNA synthesis is either active or inactive.

Here we show that the TATA-binding protein (TBP) is localized in the nucleoplasm and in the nucleolus of mammalian cells, consistent with its known involvement in transcription by RNA polymerase I, II, and III. In the nucleolus of actively growing cells, TBP colocalizes with upstream binding factor (UBF) and RNA polymerase I at the sites of rRNA transcription. During mitosis, when rRNA synthesis is down-regulated, TBP colocalizes with TBP-associated factors for RNA polymerase I (TAF(I)s), UBF, and RNA polymerase I on the chromosomal regions containing the rRNA genes. Treatment of cells with a low concentration of actinomycin D inhibits rRNA synthesis and causes a redistribution of the rRNA genes that become concentrated in clusters at the periphery of the nucleolus. A similar redistribution was observed for the major components of the rRNA transcription machinery (i.e., TBP, TAF(I)s, UBF, and RNA polymerase I), which still colocalized with each other. Furthermore, anti-TBP antibodies are shown to coimmunoprecipitate TBP and TAF(I)63 in extracts prepared from untreated and actinomycin D-treated cells. Collectively, the data indicate that in vivo TBP/promoter selectivity factor, UBF, and RNA polymerase I remain associated with both active and inactive rRNA genes.

3T3 Cells↗

PubMed1996

Screening for psychosocial problems in 4-5-year-olds during routine EPSDT examinations: validity and reliability in a Mexican-American sample.

The effectiveness of the Pediatric Symptom Checklist (PSC) as a psychosocial screening measure to meet Federal Medicaid/Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) requirements was examined in 117 low-income preschool (aged 4-5 years old) Hispanic children during well-child examinations in three clinics over an 8-month period. The PSC identified 7% of the sample as at risk for psychosocial problems. The PSC was significantly associated with parental ratings of the children's problems in functioning, with pediatric clinicians' decisions to make mental health referrals, with degrees of associations similar to those found between PSC scores, and with the same measures with school-aged children in the same clinics. Cronbach's alpha was high (r = .87) and virtually identical in English, Spanish, oral, and written formats. Although it identified a slightly lower rate of psychosocial problems in 4-5-year-olds than it had in school-aged children, the PSC appeared to provide an effective method of screening for psychosocial problems during EPSDT examinations.

California↗

PubMed1996

Pulmonary function and exercise capacity after lung resection.

The influence of pulmonary resection on functional capacity can be assessed in different ways. The aim of this study was to compare the effect of lobectomy and pneumonectomy on pulmonary function tests (PFT), exercise capacity and perception of symptoms. Sixty eight patients underwent functional assessment with PFT and exercise testing before (Preop), and 3 and 6 months after lung resection. In 50 (36 males and 14 females; mean age 61 yrs) a lobectomy was performed and in 18 (13 males and 5 females; mean age 59 yrs) a pneumonectomy was performed. Three months after lobectomy, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and maximal oxygen uptake (V'O2,max) were significantly lower than Preop values, increasing significantly from 3 to 6 months after resection. Three months after pneumonectomy, all parameters were significantly lower than Preop values and significantly lower than postlobectomy values and did not recover from 3 to 6 months after resection. At 6 months after resection significant deficits persisted in comparison with Preop: for FVC 7% and 36%, FEV1 9% and 34%, TLC 10% and 33% for lobectomy and pneumonectomy, respectively; and V'O2,max 20% after pneumonectomy only. Exercise was limited by leg muscle fatigue in 53% of all patients at Preop. This was not altered by lobectomy, but there was a switch to dyspnoea as the limiting factor after pneumonectomy (61% of patients at 3 months and 50% at 6 months after resection). Furthermore, pneumonectomy compared to lobectomy led to a significantly smaller breathing reserve (mean +/- SD) (28 +/- 13 vs 37 +/- 16% at 3 months; and 24 +/- 11% vs 33 +/- 12% at 6 months post resection) and lower arterial oxygen tension at peak exercise 10.1 +/- 1.5 vs 11.5 +/- 1.6 kPa (76 +/- 11 vs 86 +/- 12 mmHg) at 3 months; 10.1 +/- 1.3 vs 11.3 +/- 1.6 kPa (76 +/- 10 vs 85 +/- 12 mmHg) at 6 months postresection. We conclude that measurements of conventional pulmonary function tests alone overestimate the decrease in functional capacity after lung resection. Exercise capacity after lobectomy is unchanged, whereas pneumonectomy leads to a 20% decrease, probably due to the reduced area of gas exchange.

Adult↗

PubMed1996

Prognostic significance of Bcl-2 in clinically localized prostate cancer.

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. To study the prognostic significance of Bcl-2 and p53 overexpression in prostate cancer, 137 consecutive radical prostatectomy specimens were examined by immunohistochemistry. Both Bcl-2 and p53 were associated with malignant phenotype. Bcl-2 expression was more frequent in pT3 tumors (31% positive) than in pT2 tumors (5% positive, P = 0.001). p53 overexpression (found in 8%) was associated with high Gleason score (P = 0.03) and increased tumor growth fraction (Ki67 labeling index (LI); P = 0.017). Survival analysis showed that Bcl-2 expression (P = 0.03), high Ki67 LI (P = 0.018), high grade (P = 0.0037), advanced local stage (P = 0.0005), and positive lymph nodes (P = 0.026) were predictors of progression. The combined analysis of Ki67 LI and Bcl-2 allowed the distinction of three groups with different clinical outcome. Prognosis was best in Bcl-2-negative tumors with low Ki67 LI, worst in Bcl-2-positive tumors with high Ki67 LI, and intermediate in the remaining tumors (P = 0.03). These data suggest that altered expression of both Bcl-2 and p53 play a role in prostate cancer progression. Combined analysis of factors regulating both apoptosis and cell proliferation may be relevant in prostate cancer.

Aged↗

PubMed1996

[Hearing handicap--an addition to audiometric hearing loss. Results of an exploratory study of auditory communication disorders in the elderly].

Hearing problems in elderly patients cannot be evaluated completely with conventional audiological tests in most cases. Two hundred and one subjects aged 60 years or more complaining of hearing problems were studied. The following tests were employed: pure-tone audiometry, the "Basler Satztest" (a German version of the SPIN-test assessing speech perception in noise), and a German version of a "Hearing Handicap Inventory for the Elderly" (HHIE). These latter versions were developed in our institution. An auditory handicap was found in one-third of subjects with mild hearing losses (PTA < 30 dB; n = 135) and in two-thirds of subjects with greater hearing losses (PTA > and = 30 dB; n = 65). The relatively weak correlations of the pure-tone audiogram (r = 0.49) or speech audiometry (r = 0.41) with HHIE indicate that more than 50% of the variance of the hearing handicap was due to non-audiologic factors. For this reason, we recommend that the handicap questionnaire be added to the audiometric evaluation.

Aged↗

PubMed1995

Structural evolution of the Drosophila 5S ribosomal genes.

We compare the 5S gene structure from nine Drosophila species. New sequence data (5S genes of D. melanogaster, D. mauritiana, D. sechellia, D. yakuba, D. erecta, D. orena, and D. takahashii) and already-published data (5S genes of D. melanogaster, D. simulans, and D. teissieri) are used in these comparisons. We show that four regions within the Drosophila 5S genes display distinct rates of evolution: the coding region (120 bp), the 5'-flanking region (54-55 bp), the 3'-flanking region (21-22 bp), and the internal spacer (149-206 bp). Intra- and interspecific heterogeneity is due mainly to insertions and deletions of 6-17-bp oligomers. These small rearrangements could be generated by fork slippages during replication and could produce rapid sequence divergence in a limited number of steps.

Animals↗

PubMed1995

Results of surgical revascularization in ischaemic heart failure without angina.

Seventeen patients with severe ischaemic heart failure without angina were studied prospectively to determine the effects of surgical revascularization on exercise tolerance, peak oxygen consumption and left ventricular function at rest and during inotropic stimulation at 3 months after surgery. Suitability for surgery was assessed by the presence of ischaemia identified by thallium scintigraphy and stress electrocardiographic (ECG) testing and the left ventricular response to dobutamine measured by radionuclide ventriculography. One patient died awaiting surgery and one required cardiac transplantation. Fifteen patients underwent coronary artery surgery with two perioperative deaths. Thirteen patients were restudied 3 months after surgery. Mean treadmill exercise time (362 +/- 204 s to 562 +/- 303 s, P < 0.05) and peak oxygen consumption (14.9 +/- 3.5 ml/kg per min to 20.8 ml/kg per min, P < 0.01) increased significantly. Resting ejection fraction was not changed after surgery (20 +/- 5% to 21 +/- 6%) but ejection fraction during derived from thermodilution Swan-Ganz catheter data both at rest during dobutamine stimulation were unchanged after surgery. At 13 +/- 3 months after surgery there had been three sudden deaths and one patient had undergone successful cardiac transplantation. Of the remaining nine patients, three had improved to NYHA symptomatic class I, three were in NYHA class II and three in NYHA class III. Repeat treadmill exercise testing in seven patients showed that the improvement in exercise capacity evident in the first follow-up visit was maintained during long-term follow-up.

Adult↗

PubMed1995

Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies.

The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells due to the expression of the PML-RAR alpha hybrid. Here we report that adenovirus infection causes a drastic redistribution of PML from spherical nuclear bodies into fibrous structures. The product encoded by adenovirus E4-ORF3 is shown to be responsible for this reorganization and to colocalize with PML into these fibers. In addition, we demonstrate that E1A oncoproteins concentrate in the PML domains, both in infected and transiently transfected cells, and that this association requires the conserved amino acid motif (D)LXCXE, common to all viral oncoproteins that bind pRB or the related p107 and p130 proteins. The SV-40 large T antigen, another member of this oncoprotein family is also found in close association with the PML nuclear bodies. Taken together, the present data indicate that the subnuclear domains containing PML represent a preferential target for DNA tumor viruses, and therefore suggest a more general involvement of the PML nuclear bodies in oncogenic processes.

Adenovirus E1A Proteins↗

PubMed1995

Exercise capacity as a predictor of postoperative complications in lung resection candidates.

Exercise testing with measurement of maximal oxygen uptake (VO2max) is increasingly used in the assessment of lung resection candidates, but its predictive value for postoperative complications remains controversial. We therefore sought to determine the prognostic value of VO2max compared with other pulmonary function tests. A consecutive group of 80 patients (mean age 61 yr; 57 males and 23 females) scheduled for lung resection (62 malignancies, 12 benign disorders, and 6 carcinoids) underwent pulmonary function tests and symptom-limited cycle ergometry. All patients underwent lung resections: 21 pneumonectomies, 45 lobectomies, and 14 segmental or wedge resections. Group A (64 patients, 80%) had an uneventful postoperative course, whereas Group B (16 patients, 20%) had complications; 3 of them died (4% overall mortality rate). In a stepwise logistic regression analysis used to determine independent risk factors for postoperative complications (within 30 d), VO2max expressed as a percentage of predicted (84 +/- 19 for Group A versus 61 +/- 11 for Group B) proved to be the best predictor (predictive value 85.5%). Although VO2max expressed in absolute values (ml/kg/min) was also highly predictive (79.5%), a ROC curve analysis proved the percentage predicted values to be significantly more sensitive. Of 9 patients with a VO2max < 60% of predicted, 8 had complications, including all 3 patients who died after resections of more than one lobe (sensitivity 50%, specificity 98%). The estimated probability (probit model SAS software package) of suffering no complication was 0.9 for VO2max > 75% of predicted and 0.1 for a VO2max < 43%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse.

Axonal navigation during development requires that cues present in the extracellular environment be capable of modifying the structure of the cone in a dynamic way. Protein kinase C (PKC) has long been suspected to be one of the multiple molecular relays present in the terminal structure of the developing axon and involved in the transduction of extracellular signals. The latter proposal is, however, based on the use of drugs or of protocols leading to pleiotropic and often nonspecific effects. In the present study, we have taken advantage of the discovery of a peptide capable of translocating across biological membranes and to accumulate in the cytoplasm and nucleus of cells in culture, to internalize a highly specific peptidic inhibitor of PKC. We demonstrate that linking the two peptides (vector and PKC inhibitor) allows the internalization of the latter in live cells, specifically inhibits PKC and provokes a rapid modification of growth cone morphology. This set of data thus establishes that a peptidic inhibitor of PKC activity, once internalized, provokes a change in growth cone morphology, reminiscent of the collapse phenotype. In addition, the present study describes a new efficient and harmless way to introduce pharmacologically active substances in neural cells in culture.

Amino Acid Sequence↗

PubMed1995

Vitamin E and vitamin A concentrations in plasma adjusted for cholesterol and triglycerides by multiple regression.

The plasma concentration of vitamins A and E varies with the amount of concurrent lipids and thus requires lipid standardization. The present study compares a new multiple regression-based method for adjusting vitamins A and E concentrations for cholesterol and triglycerides with previous methods (adjustment for cholesterol only, and adjustment for the sum of cholesterol and triglycerides). The results show that the new method can reduce influence of the concurrent lipids.

Adult↗

PubMed1994

Major cell surface-located protein substrates of an ecto-protein kinase are homologs of known nuclear proteins.

Cell surface polypeptides serve as substrates for a casein kinase-like ecto-protein kinase activity which is demonstrable under stringent criteria with intact cells using micromolar levels of extracellular [gamma-32P]ATP. Two major 32P-labeled proteins, designated as pp100 and pp120 after their apparent molecular masses on SDS-PAGE under reducing and nonreducing conditions, have repeatedly appeared in the phosphoprotein spectra of different cell types. We have chosen HeLa cells as a source for the biochemical characterization and isolation of pp100 and pp120. Phosphorylation of pp100 and pp120 occurs in their extracellular domains at seryl residues of amino acid side chains. Several criteria deduced from the heparin sensitivity of the ecto-protein kinase and its substrate-induced shedding into the cell supernatant indicated that surface phosphorylation is a function of the ecto-protein kinase. The radioactive phosphorylation of pp100 and pp120 which coincides with their biotinylation on 2D-blots can be reversed by mild trypsination of intact cells. Purification and enrichment of pp100 and pp120 were achieved on the basis of radioactivity detection on and isolation from 1D- and 2D-gels. Amino acid sequence analysis performed on tryptic digests of purified ecto-phosphoproteins in most cases showed significant consensus sequences between pp100 and the nuclear RNA-binding protein nucleolin while pp120 sequences proved to be related to hnRNP U, a nucleoplasmic pre-mRNA-binding protein. Immunochemical analysis using anti-nucleolin and anti-hnRNP U antibodies combined with comparative phosphorylation and characterization of the ecto-proteins with authentic nucleolin and hnRNP U further established the close relationship, suggesting surface membrane versions of the nuclear proteins.

Amino Acid Sequence↗

PubMed1994

The distribution of BrK alpha/RbK alpha peak intensity ratio in human whole blood samples. Comparison between normal and colorectal cancer cases.

A preliminary study was conducted to compare the BrK alpha/RbK alpha peak intensity ratio in colorectal cancer (CRC) patients and healthy subjects (controls) in Israel. Blood samples were obtained from 61 CRC patients and 124 controls. The controls represent a normal population from different areas in Israel. Three hundred microliters of wet whole blood samples were analyzed by the EDXRF method. A weighted mean of 2.45 +/- 0.38 Br/Rb ratio was obtained for CRC patients, as compared with 3.28 +/- 0.40 Br/Rb ratio for controls. The mean value for controls represents only 112 subjects, since 12 individuals of the control group suffered from some other diseases and therefore were not included for the mean value calculation in this group. The results indicate that the Br/Rb ratio in CRC patients is significantly lower (p < 0.05) than in controls. No significant difference was found in Br/Rb ratio correlated to age and sex. It was not possible to draw final conclusion concerning the relationship between the Br/Rb ratio and the malignancy stage, since there was a relatively small number of cases in each stage under investigation.

Adult↗