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Biomedical subjects

S Perdue

Publications and source records attributed to S Perdue.

At least 19 recordsLinked to original sources
PubMed1999

Modification of non-conservative double-strand break (DSB) rejoining activity after the induction of cisplatin resistance in human tumour cells.

The induction of collateral radioresistance after the development of cisplatin resistance is a well-documented phenomenon; however, the exact processes that are responsible for the cisplatin-induced radioresistance remain to be elucidated. There was no obvious difference in the level of radiation-induced DNA double strand breaks (DSBs), in DSB rejoining rates, or the level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in the cisplatin- and radiation-sensitive 2780/WT and cisplatin-resistant 2780/CP cell lines. However, there was a significantly (P < 0.01) lower level of DSB misrejoining activity within nuclear protein extracts derived from the cisplatin- and radiation-sensitive 2780/WT and OAW42/WT tumour cell lines than in similar extracts from their cisplatin- (and radiation-) resistant 2780/CP and OAW42/CP counterparts. All of the DSB misrejoining events involved deletions of between 134 and 444 bp that arose through illegitimate recombination at short repetitive sequences, such as those that arise through non-homologous repair (NHR). These data further support the notion that the radiosensitivity of DSB repair proficient human tumour cell lines may be partly determined by the predisposition of these cell lines to activate non-conservative DSB rejoining pathways. Furthermore, our data suggest that the induction of acquired cisplatin resistance is associated with a two- to threefold decrease in the activity of a non-conservative DSB rejoining mechanism that appears to be a manifestation of NHR.

Chromosome Inversion↗
PubMed1998

Paclitaxel is preferentially cytotoxic to human cervical tumor cells with low Raf-1 kinase activity: implications for paclitaxel-based chemoradiation regimens.

BACKGROUND AND PURPOSE: Low Raf- kinase activity has been reported to be associated with radioresistance in epithelial tumor cell lines and with paclitaxel sensitivity in cervical tumor cells. Paclitaxel might thus be effective in eliminating radioresistant clones from cervical tumors, even in the absence of synergistic interaction between these therapeutic modalities. We thus established the relationship between Raf-1 kinase activity and radiosensitivity in human cervical tumor cells and determined if paclitaxel is preferentially cytotoxic to radio-resistant tumor clones. MATERIALS AND METHODS: We established and contrasted the radiation and paclitaxel sensitivity of 12 human cervical tumor clones that exhibited a wide range of Raf-1 kinase activity. RESULTS: Raf-1 kinase activity was inversely correlated (P = 0.001) with SF2 values in the 12 cervical tumor clones studied. Paclitaxel was preferentially cytotoxic to radioresistant tumor clones, with the level of paclitaxel-induced cytotoxicity being significantly (P = 0.0016) influenced by Raf-1 kinase activity levels. CONCLUSIONS: Our in vitro data indicate that there are marked, but completely opposite, Raf-1 kinase dependencies of radiation and paclitaxel cytotoxicity in cervical tumor cells. The use of combined paclitaxel and radiotherapy treatment may thus lead to higher local control rates for squamous cell carcinoma of the cervix. Circumstantially, our data suggest that the greatest therapeutic gains might accrue if paclitaxel was administered when there is the greatest proportion of tumor clones with low Raf-1 kinase activity. It may thus be desirable to use paclitaxel towards the end of radiotherapy treatment or post-radiotherapy as consolidation therapy.

Antineoplastic Agents, Phytogenic↗
PubMed1998

High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced cytotoxicity.

Paclitaxel (Taxol) is becoming increasingly important in the treatment of many tumors, although a large proportion of tumors fail to respond to this drug. The identification of the processes that confer cellular paclitaxel resistance could provide potential targets for novel therapies that may help to eliminate paclitaxel-resistant tumors. Recent reports suggest that the Raf-1 protein kinase may have a profound influence on the level of paclitaxel-induced apoptosis. We have critically evaluated the relationship between Raf-1 kinase activity and de novo paclitaxel resistance in early-passage human cervical tumors. In the 12 cell lines studied, Raf-1 kinase activity was inversely correlated (P = 0.0016) with the level of cytotoxicity induced by 60 nM paclitaxel. The relationship between these two parameters seems to be more than an epiphenomenon, because genetic down-regulation of Raf-1 kinase activity led to an approximately 4-fold increase in paclitaxel-induced cytotoxicity. The data from both our transfection studies and those on the 12 unperturbed cell lines are consistent with Raf-1 kinase being a negative determinant of paclitaxel-induced cytotoxicity. Because the cytotoxicity of paclitaxel is primarily attributable to apoptosis, these data suggest that Raf-1 kinase acts to suppress paclitaxel-induced apoptosis. These data suggest that the clinical effectiveness of paclitaxel could be substantially improved by the use of Raf-1 kinase inhibitors, provided that a similar relationship between Raf-1 kinase activity and paclitaxel cytotoxicity exists in the clinic, especially in those tumor sites where paclitaxel is the current treatment of choice e.g., ovarian and breast cancer.

Antineoplastic Agents, Phytogenic↗
PubMed1992

Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect. A review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study.

A 1975 report stated that a schizophrenic genotype may be manifested in infants by a neurointegrative defect called pandysmaturation. Recent evidence supports this: (1) 12 studies found delayed development in schizophrenics' infants and in preschizophrenics; (2) "blind" psychometric evaluations favored an adult schizotypal disorder in four to six of seven high-risk subjects with pandysmaturation in the New York study; and (3) finally, in a partial replication of this method using the Jerusalem data, blind diagnoses of "probable" and "possible" pandysmaturation were significantly related to a parental diagnosis of schizophrenia and to cognitive and motor neurointegrative deficits at 10 years. Obstetrical complications were unrelated to diagnosis, pandysmaturation, or outcome in the overall sample. However, we found a small subgroup of schizophrenic offspring in whom the most severe motor deficits at follow-up were related to obstetrical complications, pandysmaturation, and low birth weight.

Adult↗
PubMed1990

A quantitative study of dendrite complexity in selected areas of the human cerebral cortex.

This study seeks relationships between the degree of dendrite complexity of four areas of the human cerebral cortex and the type of function subserved by those areas. Quantitative studies of basilar dendrite patterns in the trunk and hand-finger receptive zones of areas 3 and 1, superior gyrus of the prefrontal cortex (area 9), and supramarginal gyrus (area 39) of the parietal lobe, in the left hemisphere of 10 subjects are reported. Measurements of dendrite complexity were based on the Sholl method of counting dendrite intersections with a series of superimposed concentric rings centered on the middle of the neuron soma. The data were analyzed graphically to show (1) characteristic dendrite profiles generated by cells in each of these areas, (2) comparisons between dendrite systems of two paired areas, i.e., trunk vs. hand-finger, and hand-finger vs. supramarginal, and (3) cumulative dendrite-ring intersection patterns for all areas studied. The data provided only partial support for our working hypothesis suggesting a relationship between complexity of the dendrite arbor and the nature of the computational tasks performed by the area. However, complexity of dendrite systems in the trunk area was found to be generally less than that of any other. In addition, there were suggestive associations between the complexity of dendrite systems of the hand-finger zone of the primary sensory receptive area and the nature of the work with which the individual had been associated during his/her working life. It proved more difficult to discern relationships between structure and function in the cortical associative areas. The study underlines the large degree of interindividual variation in dendrite structure and the need for much more extensive information about the life history of individuals who serve as subjects for this type of study.

Aged↗
PubMed1990

Formal thought disorder in childhood onset schizophrenia and schizotypal personality disorder.

The Kiddie Formal Thought Disorder Rating Scale (K-FTDS) was examined in a sample of 29 schizophrenic, 10 schizotypal, and 54 normal children, aged 5-12.5 yrs. The schizophrenic and schizotypal children had significantly more illogical thinking and loose associations than the normal children. There were no significant differences between the illogical thinking and loose associations ratings of the schizophrenic and schizotypal children. Young schizophrenic, schizotypal, and normal children had more illogical thinking and loose associations than older children in their respective groups. The diagnostic, developmental, and cognitive implications of the study's results are discussed.

Association↗
PubMed1988

Amniotic fluid-AFP in Down syndrome and other chromosome abnormalities.

80.2 Per cent of 111 Down syndrome pregnancies had anmiotic fluid (AF) alpha fetoprotein (AFP) levels on or below the median and 10.8 per cent at or below 0.5 MoM compared with 41.9 and 1.4 per cent of controls. These differences were even more striking when the gestational age was less than 18 weeks compared with greater than or equal to 18 weeks. No such association was seen for other chromosome abnormalities including trisomy 18,45,X and mosaics, 47,XXY,47,XXX, and other structural abnormalities and triploidy, even when high levels due to defects such as omphalocele and cystic hygroma were excluded. All cases of trisomy 13 and 80 per cent with 47,XYY had AF-AFP levels above the median. Selection of cases for karyotyping by a low level of AF-AFP would clearly fail to detect aneuploidies other than Down syndrome and is not recommended. A possible weak association between low maternal serum (MS) and AF-AFPs in Down syndrome was most evident at less than 18 weeks, suggesting that MS screening between 16 and 18 weeks may be the most informative time.

Adult↗
PubMed1987

Application of meta-analysis using an electronic spread sheet to exercise testing in patients after myocardial infarction.

Decision analysis is being applied to medical practice in order to achieve cost efficacy in health care delivery. Critical to this process is establishing the diagnostic and prognostic accuracy of medical tests and the effectiveness of interventions. Meta-analysis is an approach that applies statistical methods to groups of studies in order to extract consensus results. Electronic spreadsheets facilitate meta-analysis with their ability to store, sort, graph, and mathematically manipulate both the methodologic approaches and clinical findings of seemingly disparate studies. As an example, this application is demonstrated with an analysis of studies that were performed to evaluate the prognostic value of exercise testing in patients recovering from a myocardial infarction. The following conclusions were reached: (1) patients excluded from exercise testing have the highest mortality; (2) only subsets of patients have been tested resulting in highly selected patient samples that make findings difficult to generalize; (3) of the five exercise test responses, only an abnormal systolic blood pressure response and a poor exercise capacity predicted risk more frequently than by chance; (4) submaximal or predischarge testing has greater predictive power than postdischarge or maximal testing; and (5) exercise-induced ST segment depression only appears to be predictive of increased risk in patients with inferior-posterior myocardial infarctions. This approach to combining studies is important since even careful analysis of a single study cannot elucidate all of the complex interactions and selective biases that have occurred. However, comparison of many heterogeneous studies is at best an arduous and time-consuming task. This approach to using electronic spreadsheets to collate and analyze multiple studies facilitates recognition of the population characteristics, clinical factors, and methodologic considerations that affect outcome and allows the quick inclusion of additional studies for re-analysis and interpretation.

Blood Pressure↗
PubMed1986

Platelet MAO and measures of attention and impulsivity in boys with attention deficit disorder and hyperactivity.

Platelet monoamine oxidase (MAO) activity was studied in 22 boys diagnosed as having attention deficit disorder with hyperactivity and 12 healthy control boys admitted to a clinical research center and placed on a diet low in monoamines. The hyperactive boys had lower platelet MAO activity than controls, and MAO activity was related to performance on the Matching Familiar Figures Test (MFF) and the Continuous Performance Test (CPT), which yield scores sensitive to impulsivity and inattention. Furthermore, it was negatively related, in hyperactive boys only, to two tests of reading and spelling achievement. Administration of d-amphetamine and placebo in a double-blind crossover design did not significantly raise MAO levels above baseline and was minimally related to improved performance on the MFF and CPT.

Achievement↗
PubMed1986

Combining maternal age and serum alpha-fetoprotein to predict the risk of Down syndrome.

Twenty-eight cases of Down syndrome with maternal serum alpha-fetoprotein (AFP) measured at second trimester were added to 137 previously reported cases. Seventy-eight percent of affected pregnancies had levels at or below the median AFP value, compared with 50% of unaffected pregnancies. Maternal age at delivery and serum AFP levels by multiples of the median were used to construct a table to determine the risk of Down syndrome. This was compared with the risk for a 35-year-old woman (one in 365). Similar risks were estimated for a 21-year-old with AFP below 0.4 multiples of the median, a 23-year-old below 0.5, a 26-year-old below 0.6, and a 29-year-old below 0.7 multiples of the median. This study provides guidelines for counseling pregnant women who have low serum AFP levels.

Adult↗
PubMed1985

Preferential effectiveness of cyclosporin in patients receiving kidney transplants after glomerulonephritis.

Glomerulonephritis patients transplanted with cadaver kidneys had a significantly higher one-year graft survival when immunosuppressed with cyclosporin rather than standard therapy (80% versus 59%, p less than 10(-5]. For nephrosclerosis patients the corresponding rates were 70% and 59% (p greater than 0.05); and in those with antecedent diabetes mellitus, polycystic kidney, and pyelonephritis the differences were negligible. In glomerulonephritis patients, but not in the other groups, cyclosporin was additive to the effect of transfusions and of HLA-A, B and HLA-Dr matching.

Cyclosporins↗
PubMed1984

Increased vulnerability of the donor organ in related kidney transplants for certain diseases.

The one-year kidney transplant survival rates from parental donors into recipients with pyelonephritis (PN) was 79% as compared with the low rate of 62% for polycystic disease (PC) and diabetes mellitus (DM). Even more striking was the 42% one-year graft survival in systemic lupus erythematosus (SLE) patients receiving parental donor grafts. HLA-identical sibling donor transplants into patients with DM had a low survival rate of 75% as compared with 90% in PN patients. These results were analyzed for interactions of donor type and disease by comparing the relative survival rates among types of donors within each recipient disease. After taking into account higher overall risks attributable to medical complications inherent in the different disease categories, related donor grafts into patients with PC, SLE, and DM have lower graft survival rates than would be expected from differences in cadaver donor rates by disease. In practical terms, for related donor transplants into patients with SLE, DM, and PC, it may be necessary to consider the vulnerability of the donor organ as another factor.

Cadaver↗
PubMed1982

HLA-DR3 associated with improved kidney transplant survival.

Using the National Kidney Recipient Pool and selecting all patients who were HLA-DR typed, immunized by either transfusion or kidney allograft, and had recorded cytotoxic antibody against a panel of lymphocytes, we found significantly lower levels of cytotoxic antibody in patients with HLA-DR3 (p less than 0.05). Moreover, when we examined patients with only HLA-DR3 (presumed homozygous) we found that the low response effect was even stronger and was significant at 30%, 67%, or 90% cytotoxic antibody cutoffs. One of the immediate predictions of postulating that homozygous HLA-DR3 patients are low responders is that these patients should have better kidney transplant survival. Indeed, when we examined transplant survival in HLA-DR3 homozygous transplant patients and non-HLA-DR3 patients, the 1-year survival was 74% +/- 9% vs. 49 +/- 4%, respectively. When one stratifies the data for transfusion effect, the 0-4 transfusion category shows 43% +/- 5% survival for non-HLA-DR3 recipients vs. 79% +/- 10% for HLA-DR3 only recipients. These data strongly suggest HLA-DR3 individuals have a low responsiveness to histocompatibility antigens.

Antilymphocyte Serum↗