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Biomedical subjects

J Arnold

Publications and source records attributed to J Arnold.

At least 55 records · Page 3Linked to original sources
PubMed2000

Symbiont survival and host-symbiont disequilibria under differential vertical transmission.

Interspecific genetic interactions in host-symbiont systems raise intriguing coevolutionary questions and may influence the effectiveness of public health and management policies. Here we present an analytical and numerical investigation of the effects of host genetic heterogeneity in the rate of vertical transmission of a symbiont. We consider the baseline case with a monomorphic symbiont and a single diallelic locus in its diploid host, where vertical transmission is the sole force. Our analysis introduces interspecific disequilibria to quantify nonrandom associations between host genotypes and alleles and symbiont presence/absence. The transient and equilibrium behavior is examined in simulations with randomly generated initial conditions and transmission parameters. Compared to the case where vertical transmission rates are uniform across host genotypes, differential transmission (i) increases average symbiont survival from 50% to almost 60%, (ii) dramatically reduces the minimum average transmission rate for symbiont survival from 0.5 to 0.008, and (iii) readily creates permanent host-symbiont disequilibria de novo, whereas uniform transmission can neither create nor maintain such associations. On average, heterozygotes are slightly more likely to carry and maintain the symbiont in the population and are more randomly associated with the symbiont. Results show that simple evolutionary forces can create substantial nonrandom associations between two species.

Genetic Heterogeneity↗
PubMed2000

Susceptibility testing of Haemophilus influenzae to clarithromycin.

Susceptibility testing of Haemophilus influenzae to the macrolide compounds has often been problematic. This is as a result of the inability of many isolates of H. influenzae to grow without the addition of 5% CO2 to the incubation atmosphere and the subsequent detrimental effect that CO2 has on the activity of the macrolide group of compounds. This report describes refinements and recommendations for susceptibility testing of H. influenzae to the macrolide clarithromycin.

Anti-Bacterial Agents↗
PubMed2000

DNA microsatellite instability and mismatch repair protein loss in adenomas presenting in hereditary non-polyposis colorectal cancer.

BACKGROUND AND AIM: Hereditary non-polyposis colorectal cancer (HNPCC), as its name implies, is associated with few adenomas, and the early evolution of colorectal neoplasia is poorly understood. In this study our aim was to clarify the genetic profiles of benign polyps in subjects with HNPCC using a combined molecular and immunohistochemical approach. METHODS: Thirty adenomas and 17 hyperplastic polyps were obtained from 24 affected HNPCC subjects. DNA was extracted from paraffin embedded tissue by microdissection and analysed for the presence of microsatellite instability (MSI) and mutations in five genes known to be targets in mismatch repair deficiency (TGFbetaRII, IGF2R, BAX, hMSH3, and hMSH6). Serial sections were stained by immunohistochemistry for hMLH1 and hMSH2. RESULTS: Twenty four (80%) of 30 adenomas showed MSI. Of MSI positive adenomas, 66.7% showed MSI at more than 40% of markers (high level of MSI (MSI-H)). Two of 17 hyperplastic polyps revealed MSI at one marker (low level of MSI (MSI-L)). A significant association was found between MSI-H and high grade dysplasia in adenomas (p=0.004). Eight of nine adenomas with mutations of coding sequences revealed high grade dysplasia and all nine were MSI-H. Four of the nine ranged in size from 2 to 5 mm. The presence of the hMSH6 mutation was significantly correlated with high levels of MSI (80% of markers) (p<0.02). Twenty four adenomas gave evaluable results with immunohistochemistry. One of six (17%) microsatellite stable, six of seven (86%) MSI-L, and 11 of 11 (100%) MSI-H adenomas showed loss of either hMLH1 or hMSH2. CONCLUSIONS: Most adenomas in subjects with a definite diagnosis of HNPCC show MSI (80%). The finding of MSI-L is usually associated with loss of expression of hMLH1 or hMSH2, unlike the situation in MSI-L sporadic colorectal cancer. The transition from MSI-L to MSI-H correlated with the finding of high grade dysplasia and mutation of coding sequences and may be driven by mutation of secondary mutators such as hMSH3 and hMSH6. Advanced genetic changes may be present in adenomas of minute size.

Adenoma↗
PubMed2000

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells.

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1). The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5-7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.

Cell Survival↗
PubMed2000

Perforin-mediated lysis of tumor cells by Mycobacterium bovis Bacillus Calmette-Guérin-activated killer cells.

Immunotherapy with Bacillus Calmette-Guérin (BCG) is clinically established in the treatment of superficial bladder cancer. In our attempt to clarify the underlying immunological mechanism, we could previously show that stimulation of PBMC with BCG leads to the generation of cytotoxic BCG-activated killer (BAK) cells. Among others, these BAK cells as well as lymphokine-activated killer (LAK) cells have been suggested as possible effector cells during BCG therapy. To understand BCG-induced activation of effector lymphocytes more precisely, we investigated the lytic pathways of human BAK cells and compared BAK cell cytotoxicity with LAK cell cytotoxicity. Perforin and Fas ligand (FasL) are the major cytolytic molecules of cytotoxic lymphocytes. Our results demonstrate that BAK and LAK cells showed an increased expression of perforin and FasL as compared with unstimulated controls. Killing of T-24 bladder tumor as well as Jurkat cells by BAK and LAK cells was predominantly mediated via perforin as demonstrated by a drastically reduced lysis in the presence of concanamycin A and EGTA/MgCl2, respectively. In contrast, lysis (radioactive release assay) and membrane disintegration (Annexin V binding) of both targets by BAK and LAK cells could not be blocked with an inhibitory anti-FasL monoclonal antibody (NOK-1). Nevertheless, T-24 and Jurkat were susceptible to killing by recombinant soluble FasL and by Chinese hamster ovary cells expressing membrane-bound FasL. We conclude that cellular mediators of BCG effector mechanisms, such as BAK and LAK cells, kill their targets via perforin and independent of the FasL pathway. Because we also found increased numbers of perforin-expressing lymphocytes in patients after BCG therapy, our findings have potential clinical relevance because BCG therapy would not be impaired by FasL resistance of target cells, which recently has been described for some tumors.

Adjuvants, Immunologic↗
PubMed1999

Frequent loss of heterozygosity at 1p36 in ovarian adenocarcinomas but the gene encoding p73 is unlikely to be the target.

Loss of heterozygosity (LOH) involving the distal part of the short arm of chromosome 1 occurs frequently in ovarian adenocarcinomas but the tumour suppressor gene(s) targeted by this event is unknown. We have used five microsatellite markers in a panel of 56 ovarian adenocarcinomas to determine which part of 1p34 - 36 is the focus of this LOH. LOH was considerably more common at 1p36 (43%) than at 1p34 - 35 (18%), and 11 tumours showed LOH at 1p36 but not at 1p34 - 35. These data strongly suggest the presence of a tumour suppressor gene inactivated in ovarian adenocarcinoma at 1p36. The p53 homologue, p73, has recently been isolated and mapped to 1p36 and therefore is a candidate for this tumour suppressor gene. However, RT - PCR and Western analyses revealed strong expression of p73 in ovarian adenocarcinoma cell lines but very low or undetectable levels in normal ovarian surface epithelial cells. Immunohistochemical analysis of primary ovarian tumours showed that only 3/22 (14%) contained p73 expressing cells. There was no association between 1p36 LOH and p73 expression in ovarian tumours, nor between p73 and p53 expression. These findings strongly suggest that p73 is not the target of 1p36 LOH in ovarian adenocarcinomas but indicate the presence of an, as yet unidentified, tumour suppressor gene in this region that plays an important role in ovarian tumorigenesis.

Adenocarcinoma↗
PubMed1999

[The new International Standardization Organization 9000 norms: 2000].

The reviewing of ISO 9000 norms has been planned to be published within the last quarter of the year 2000. It aims at overcoming the limits and difficulties of use evidenced by the implementation of the 1994 ISO norms, and at providing an analysis aid for improving quality, which would be adapted to the needs of each company or user. What is at stake with these new norms is the implementation of a quality management system, and its evolution towards a total-quality management.

Certification↗
PubMed1998

Dynamics of cytonuclear disequilibria in subdivided populations.

The purpose of this report is to understand the effects of hybrid zone architecture and genetic drift on cytonuclear genotypic disequilibria. We also study the exact dynamics of the expected values of the cytonuclear genotypic disequilibria for both the homozygotes and heterozygotes in a finite population containing reproductively isolated subpopulations under random drift alone and random drift along with mutation, respectively. We study the dynamics of the between-population component of the disequilibrium for the homozygotes. The dynamics of the variances of these disequilibria under the random drift model are studied by Monte Carlo simulations. The asymptotic formulas for both the expectations and variances are obtained. The results are contrasted with those for a single undivided population and their biological significances are discussed. Approximate normality of the disequilibria measures are also demonstrated by Monte Carlo simulations.

Animals↗
PubMed1998

Higher SaO2 in chronic neonatal lung disease: does it improve sleep?

Sleep fragmentation, decreased rapid eye movement (REM) sleep time, and REM sleep hypoxemia have been reported in infants with chronic neonatal lung disease (CNLD) in early infancy despite an awake hemoglobin oxygen saturation (SaO2) >93%. Interestingly, higher inspired O2 concentrations have been demonstrated to reduce REM sleep fragmentation in CNLD patients in middle infancy. However, the effect of increased SaO2 on sleep architecture in infants with CNLD near the time of discharge from neonatal intensive care has not been reported. We performed paired overnight polysomnography in a sleep laboratory on 16 infants with CNLD (4 weeks median corrected age) in air or their usual inspired oxygen (SaO2 >93%) and again when receiving 0.25 L/min higher than baseline inspired oxygen via nasal catheters (SaO2 >97%). A control group of seven healthy preterm infants was similarly studied. For CNLD infants on supplemented O2, sleep duration decreased by 15% (422+/-66 min vs. 359+/-89 min; P< 0.005), and sleep efficiency decreased by 7% (73.2+/-10.6% vs. 66.4+/-14.0%; P < 0.005) but percentage of time in REM sleep (REM%) (31.5+/-8.9% vs. 29.8+/-8.6%; P=0.560), REM epoch duration (12.4+/-2.8 min vs. 13.4+/-4.3 min; P=0.420), and REM arousal index (18.6+/-6.5 vs. 18.8+/-7.2; P=0.990) were not significantly affected. Conversely, higher O2 did not alter sleep architecture in the control group. The mean non-REM (NREM) respiratory rate decreased (CNLD: P=0.003; controls: P=0.02), NREM SaO2 increased (P < 0.05), although the mean transcutaneous CO2 was unaltered in both CNLD and control groups. This study confirmed low REM% in CNLD infants in early infancy and demonstrated that a higher SaO2 adversely affected sleep time but did not influence REM sleep duration or arousal frequency. A target SaO2 >93% is, therefore, as efficacious as an SaO2 >97% in optimizing sleep architecture in CNLD infants.

Bronchopulmonary Dysplasia↗
PubMed1998

Sleep, respiratory rate, and growth hormone in chronic neonatal lung disease.

This study assessed whether respiratory rates (RRs) correlate with urinary growth hormone (U-GH) excretion and sleep architecture in infants with chronic neonatal lung disease (CNLD) in early (1 month), middle (6 months), and late (10 months) infancy. Twenty-three preterm infants (CNLD=16, controls=7) were studied on 51 occasions. CNLD infants were stratified according to mean non-REM sleep respiratory rate (NREM RR) in early infancy into "High RR CNLD" infants (mean NREM RR >2 SD higher than controls) and "Normal RR CNLD" infants (mean NREM RR within 2 SD of controls' mean). "High RR CNLD" infants (RR >45) had a lower mean birthweight (P=0.015), current weight (P=0.042), current length (P=0.02), and growth velocity in early infancy (grams/week gained: P=0.042) than "Normal RR CNLD" and control infants. Mean (95% CI) U-GH excretion (ng U-GH/g urinary creatinine) was higher in "High RR CNLD" infants in air or their usual O2 (1,932 [459, 3,406]) than "Normal RR CNLD" (394 [147, 642]) and controls (320 [147, 492]) (P=0.024). With resolution of tachypnea by mid-infancy, hemoglobin oxygen saturation (SaO2) >93%, mean growth parameters and U-GH excretion for the "High RR CNLD" group were not significantly different from "Normal RR CNLD" and control groups. CNLD infants demonstrated increased sleep efficiency (P=0.016), whereas controls had similar sleep efficiency between early and middle infancy (P=0.452). Mean percent time in REM sleep (REM%) and slow wave sleep (SWS%) were not significantly different between early and middle infancy and did not vary in relation to respiratory rate. We conclude that tachypneic infants with CNLD have slower growth and elevated U-GH excretion in early infancy. With resolution of tachypnea, growth improved, U-GH excretion decreased, and sleep consolidation occurred. An elevated U-GH in tachypneic CNLD infants may reflect stress, compromised nutrition (GH resistance), or a feedback loop involving a direct effect of GH on lung growth and repair.

Bronchopulmonary Dysplasia↗
PubMed1998

New reference allelic ladders to improve allelic designation in a multiplex STR system.

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples.

Alleles↗
PubMed1998

Psychosocial aspects of adolescent cancer survival.

OBJECTIVE: The purpose of this research was to examine the psychosocial status of adolescent cancer survivors and compare them with healthy peers. It has been suggested in previous research that the majority of survivors display equivalent levels of psychosocial functioning post-treatment as compared with healthy controls. However, despite successful treatment, survivors may have to adjust to living with a chronic illness and its associated late effects interspersed across the lifespan (e.g. infertility, cognitive deficits, heart complications). Whilst young people appear to have similar levels of psychosocial functioning, avoidance strategies such as denial may result in previous research findings being confounded and in underestimating the true psychosocial status of survivors. It is important to understand the psychosocial status of survivors in order to optimise their quality of life. METHODOLOGY: Coping mechanisms, anxiety levels and self-concepts of 32 adolescent cancer survivors, predominantly Acute Lymphoblastic Leukaemia (ALL) were compared with 34 healthy adolescents (age range 12-17 years), via a mailout. RESULTS: Survivors' self-reports suggest no overt psychological dysfunctioning. Whilst the two groups shared similar coping strategies, survivors were found to be less anxious than peers, with a tendency to employ avoidance strategies to deal with problems faced in adolescence. Age, gender and specific illness variables, such as age at diagnosis and time since treatment, were strong predictors of psychological outcome. CONCLUSIONS: Results can be interpreted as suggesting that whilst cancer survivors have a similar psychosocial profile to healthy peers, they are more likely to utilise avoidance strategies to manage problems.

Adaptation, Psychological↗
PubMed1998

Standardizing the classification and description of follicular unit transplantation and mini-micrografting techniques. The American Society for Dermatologic Surgery, Inc.

Previous attempts at classifying small graft transplants have focused mainly upon graft size and have not taken into consideration other technical factors involved in graft production that may influence the outcome of the surgery. The proposed classification attempts to consider these factors by including various technical aspects of harvesting, dissection, and placement, all of which impact the quality and quantity of the small grafts used in the procedure. By standardizing the nomenclature, as well as the description of the other factors involved in the surgery, communication between physicians and patients may be facilitated. In addition, different procedures may be more accurately studied and compared.

Alopecia↗