Search PubMed⌕ Search

Biomedical subjects

J Robertson

Publications and source records attributed to J Robertson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Alleles of APC modulate the frequency and classes of mutations that lead to colon polyps.

Most inherited mutant alleles of the adenomatosis polyposis coli gene (APC) cause the appearance of large numbers of colon polyps, the familial polyposis syndrome. (These mutant alleles are designated APCp alleles.) A subset of APC mutations, the attenuated or APC(AP) alleles, predispose to only a few colon polyps. This leads to the hypothesis that if mutation of the inherited normal allele is rate limiting in polyp development, the increased number of polyps associated with the APCp allele indicates that the frequency of mutations that can lead to polyp formation is higher among APCp carriers than among APC(AP) carriers. We have previously suggested that the APC protein might modulate the frequency of mutations, such as loss of heterozygosity (LOH), necessary for colon polyp formation. We thus reasoned that tumours from patients who carry an APC(AP) allele might show a reduced frequency of LOH compared with tumours from patients who carry an APCp allele. Loss of AAPC mutant alleles is designated as LOH(AP). Screening of tumours from APC(AP) carriers revealed a reduction of LOH compared with that of an unselected group of polyposis patients. In fact, no loss of the inherited APC(N) allele was observed, although sequencing showed that the inherited APC(N) allele had frequently undergone point mutations and small deletions in the tumours. A low frequency loss of the inherited APC(AP) allele was seen. These findings support the suggestion that the APC(AP) allele has residual gene activity and that this activity modulates the spectrum and frequency of mutations that lead to adenoma formation.

Adenomatous Polyposis Coli↗
PubMed1998

A dimensional classification of autism spectrum disorder by social communication domains.

OBJECTIVE: To investigate whether "social communication" could be used to assess severity of symptoms in autism spectrum disorder. Social communication refers to the communication of cognitive and emotional information through facial expression, gesture, and prosody and through implicit understanding of pragmatics and of theory of mind. METHOD: Subjects were evaluated by raters using the Autism Diagnostic interview-Revised and either the Autism Diagnostic Observation Schedule or the Pre-Linguistic Autism Diagnostic Observation Schedule. Two investigators independently diagnosed autism, Asperger's disorder, or pervasive developmental disorder-not otherwise specified in 63 subjects. Items from the Autism Diagnostic Interview-Revised that were judged to represent social communication behaviors were factor-analyzed. RESULTS: Three factors were identified: affective reciprocity, joint attention, and theory of mind. Comparing this new classification approach to DSM-IV led to suggestions for possible changes in the latter: (1) Vocabulary and grammar deficiencies in autistic persons should be coded under developmental language disorder, (2) The diagnosis of Asperger's disorder may not be needed. (3) Requiring that all persons with autism spectrum disorder have a symptom from the "restrictive, repetitive, and stereotypic" list may need to be reconsidered. CONCLUSIONS: The DSM-IV category of pervasive developmental disorder may be ideal for diagnosing "classic" autism, but it may be inadequate for diagnosing less severe forms of the disorder.

Adolescent↗
PubMed1998

A systematic review of the skeletal effects of estrogen therapy in postmenopausal women. I. An assessment of the quality of randomized trials published between 1977 and 1995.

PURPOSE: To examine the quality of published randomized controlled trials of the effects of estrogen treatment on fracture risk and measures of bone mass. DATA SOURCES: Articles on estrogen treatment for osteoporosis published between 1977 and 1995 were identified by searching Medline and Excerpta Medica databases and bibliographies of original papers and published reviews. STUDY SELECTION: Studies selected were randomized controlled trials of the efficacy of estrogens in preventing loss of bone mass or fractures in postmenopausal women. DATA EXTRACTION: Data extraction and quality assessment were performed in duplicate, with assistance of a manual. Raters were blinded as to authors and their affiliations and the publication details. RESULTS: Of 99 eligible randomized controlled trials published between 1977 and 1995, eight included no extractable data, and 23 contained results that were published in duplicate. Total quality scores increased over time, but this was accounted for by improvements only in the measurement technologies used to estimate bone mineral content or density. There was no improvement in the quality of randomization methods, the extent to which withdrawals were accounted for, or in the baseline comparability of treated and control patients. Neither sample sizes nor durations of follow-up increased over time. CONCLUSIONS: This body of literature fails to address whether estrogen therapy reduces fracture rates, and does not allow for comparison of the effects of different active therapies on change in bone density. Although there were improvements in the techniques for estimating bone mass and delivering estrogen treatment, the studies published in the 1990s were no more informative for making clinical or policy decisions than those published in the 1970s.

Adult↗
PubMed1998

A systematic review of the skeletal effects of estrogen therapy in postmenopausal women. II. An assessment of treatment effects.

PURPOSE: To combine the results of randomized controlled trials to provide overall estimates of the effect of estrogen treatment on fracture rates and measures of bone mass. DATA SOURCES: Articles on estrogen treatment for osteoporosis published between 1977 and 1995 were identified. STUDY SELECTION: Studies selected were randomized controlled trials of the efficacy of estrogens in preventing loss of bone mass or fractures in postmenopausal women. DATA EXTRACTION: Data extraction and quality assessment were performed in duplicate, with assistance of a manual. Raters were blinded as to authors and their affiliations and the publication details. With estimates of bone mass, the treatment effect size was defined as the difference in the mean annual change in bone mass between the treatment and control groups divided by the pooled standard deviation for change. In the case of fractures, efficacy was measured as the reduction in the numbers of individuals experiencing new fractures with treatment. Effect sizes were pooled using the random effects model. RESULTS: Thirty-seven studies met the criteria for inclusion in the systematic review. Only one small secondary prevention trial contained evaluable data on vertebral fractures. This study found a fracture relative risk of 0.63 (95% confidence interval, CI 0.28-1.43) with estrogen treatment. There was more information on the effects of treatment on bone mass. Overall effect sizes ranged between 0.5 and 2.5 standard deviation (SD) units for change. A dose-response relationship was apparent but high doses of estrogens were not associated with effect sizes greater than those observed with recommended doses. There was no significant difference in efficacy between transdermal and oral administration of estrogens. Pooling of paired data from secondary prevention studies indicated that treatment effect sizes were smaller at the hip (0.92, 95% CI 0.3-1.5 SD units) than at the spine (2.1, 95% CI 0.9-3.3 SD units). No significant effects of co-intervention with calcium, progestogens or androgens were seen, although an additive effect of higher doses of calcium could not be ruled out. CONCLUSIONS: Clear-cut effects of estrogens in attenuating the postmenopausal decline in estimated bone mass were apparent in this literature. However, the trials were short-term and provide inadequate evidence on the effects of treatment on fracture risk.

Dose-Response Relationship, Drug↗
PubMed1997

Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer.

Hormonal breast cancer therapies have traditionally been considered cytostatic, but recent pre-clinical data suggest that anti-oestrogens can induce apoptosis. The aim of this study was to assess whether tamoxifen (TAM) and ICI 182780 (ICI) could induce apoptosis in human breast cancer, and whether this was related to oestrogen receptor status. We measured apoptosis in primary breast cancer patients before and after pre-surgical treatment with 20 mg/day TAM (study 1) or 6 or 18 mg/day ICI (study 2). In each study there was a randomised non-treatment (NT) control group. TAM significantly increased apoptotic index (AI) in ER+ but not in ER- tumours. There was a significant increase in AI following treatment with ICI. Insufficient pairs of samples were available to determine whether this change was confined to ER+ tumours, but in a cross-sectional analysis AI was significantly higher in excision biopsies for ICI-treated than NT patients for ER+ but not ER- tumours. Our results provide clinical evidence that apoptosis may be induced in ER+ primary breast cancer by both non-steroidal and steroidal anti-oestrogens.

Adult↗
PubMed1997

Incorporation of NF-L into keratin filaments in transfected epithelial cells.

Neurofilaments are the characteristic intermediate filaments of mature neurons; during development and in some neuronal cell lines and neuroendocrine tumors, neurofilament proteins are expressed together with vimentin or cytokeratins. In some cell types, the filamentous arrays formed by neurofilaments and vimentin or cytokeratins do not coincide. However, individual neurofilament proteins co-assemble with vimentin in transfected non-neuronal cells. In order to determine whether individual neurofilament proteins could also co-assemble with cytokeratins in a cellular environment, the light chain of neurofilaments, NF-L, was transfected into MCF-7 cells, in which the only cytoplasmic intermediate filament proteins expressed are cytokeratins. In transfected MCF-7 cells, human NF-L was localized to a prominent filamentous network. This pattern most probably reflected the incorporation of NF-L into the endogenous keratin cytoskeleton as it is unlikely to be due to human NF-L self-assembly since, like its rodent counterpart, human NF-L accumulated into punctate aggregates when transiently transfected in intermediate filament-deficient SW13 vim- cells. These results suggest the existence of a specific mechanism of segregation of neurofilaments and keratin filaments in some cell types.

Epithelium↗
PubMed1997

Exposure of tilapian fish to the pesticide lindane results in hypocellularity of the primary hematopoietic organ (pronephros) and the spleen without altering activity of phagocytic cells in these organs.

Tilapia were dosed by intraperitoneal injection for 5 consecutive days with either 20 or 40 mg/kg of the environmental contaminant hexachlorocyclohexane (lindane). The effects of this organochlorine pesticide on morphology and total cellularity of the spleen and pronephros were examined on the second day following termination of dosing. The functional capacity of phagocytic cells isolated from both spleen and pronephros was also evaluated as possible additional indicators of chemical-induced immunotoxicity. A dose-related reduction was found in spleen and pronephros total white blood cell counts in the fish exposed to lindane. In addition, hypocellularity of lymphoid regions in the spleen and pronephros was evident in chemical-exposed animals upon histopathological examination. However, phagocytosis of fluorescent microspheres by phagocytic cells isolated from the spleen and pronephros was not inhibited by the exposure to lindane. Similarly, no decrease in phorbolmyristate acetate (PMA)-stimulated hydrogen peroxide production was observed in phagocytic cells collected from lindane-exposed fish. These results suggest that cellular depletion in tilapia spleen and pronephros may represent a more sensitive indicator of lindane exposure than does the functional capacity of phagocytic cells isolated from these hematopoietic organs. Ultrastructural observations support this hypothesis and, further, suggest that lymphocytic cells may be targeted at the present exposure levels.

Animals↗
PubMed1997

Doppler index perfusion in the detection of hepatic metastases secondary to gastric carcinoma.

BACKGROUND: The early detection of liver metastases in patients with gastric carcinoma is important for determining the appropriate therapy; however conventional imaging techniques are limited for detecting "occult" liver metastases. Previous studies have shown that the measurement of the Doppler perfusion index (DPI)-ratio of hepatic arterial to total liver blood flow-can detect the presence of even small hepatic tumors. In this study, we compared the measurement of DPI with computed tomography (CT) for detecting gastric liver metastases. METHODS: At presentation, 43 patients with gastric carcinoma underwent CT scanning of the liver and after 12 hours of fasting, DPI measurement was carried out using Doppler sonography. RESULTS: Both techniques detected overt liver metastases in 9 of the 43 patients. Of the 34 remaining patients with an apparently disease-free liver on the basis of CT, laparotomy, or laparoscopy, 14 subsequently develop liver metastases over a follow-up period of 4 years, 13 of which had been predicted by DPI at the time of presentation. CONCLUSION: The data suggest that the measurement of the DPI is more sensitive than a CT scan for detecting liver metastases secondary to gastric carcinoma.

Aged↗
PubMed1997

Natural protection of spring and well drinking water against surface microbial contamination. II. Indicators and monitoring parameters for parasites.

Recent outbreaks of cryptosporidiosis and reports of other newly described para-sitic diseases associated with drinking water transmission prompted a reevaluation of source water monitoring criteria for public health protection. The field of microbial indicators was reviewed and each candidate sentinel evaluated in terms of its sensitivity, specificity, and technical feasibility. In addition, a clear distinction was made between source water monitoring and monitoring in the distribution system. Of all potential candidate microbial sentinels, Escherichia coli is deemed the most efficacious for public health protection. Based on a conservative estimate of its half-life in groundwater for 8 d, it is recommended that at least two samples be obtained during this half-life. In addition to E. coli, two water quality indicator sentinels, which are not necessarily direct public health threats, should also be monitored at the same frequency. These are the total coliform group and the enterococci. If E. coli is present in any source water sample, the borehole and any directly connected borehole should be embargoed. If either total coliforms or enterococci are detected, only that individual borehole should be taken off line and not used until the situation is remediated and the cause of the fecal contamination eliminated. Clostridium perfringens spores serve as a useful long-lived indicator. However, their perseverance in a sample should not be considered a direct public health threat because spores may far outlive pathogens. As a parasite indicator, C. perfringens should have the same importance as a positive coliform or enterococcus analysis. Coliphages do not yet fulfill enough of the criteria to be routinely employed. Biological monitoring should be coupled with physicochemical monitoring to establish a long-term history of the source. Because all natural waters vary in the amounts of heterotrophic plate count bacteria, test methods should be employed that are refractory to them. A combination of rigorous source protection plus extraordinary source monitoring serve as sufficient multiple barriers for parasite protection.

Animals↗
PubMed1997

Twin zygosity. Automated determination with microsatellites.

OBJECTIVE: Twin zygosity determinations can be performed with anthropologic, serologic and genetic markers; however, these methods are more than occasionally inefficient, often expensive and sometimes inaccurate. We used microsatellites as DNA markers and developed a largely automated, rapid and efficient method of determining zygosity. STUDY DESIGN: We used five highly polymorphic short tandem repeat loci, coamplified by polymerase chain reaction (PCR) using fluorescence-labeled primers. Thirty-six samples were simultaneously analyzed by electrophoresis and laser detection. The PCR products were sized by automated fragment analysis. RESULTS: We typed 132 pairs of monozygotic (MZ) and dizygotic (DZ) twins. With five markers, the probability that any twin pair was MZ if all markers were concordant was 99%. CONCLUSION: This method is a rapid and reliable approach to zygosity detection.

Adult↗
PubMed1997

High resolution protein electrophoresis of equine cerebrospinal fluid.

OBJECTIVE: To determine normal CSF electrophoresis patterns in horses, and to determine whether the electrophoretic scans from horses with cervical compression differ from those of neurologically normal horses. ANIMALS: 32 horses assigned to 1 of 2 groups: neurologically normal (n = 18) or cervical compression (n = 14). PROCEDURE: CSF was collected from 18 neurologically normal horses referred to the Marion duPont Scott Equine Medical Center, and protein electrophoresis was performed to describe the normal equine CSF electrophoretogram. Results of CSF electrophoresis from 14 horses with cervical compression were then compared with results for the neurologically normal horses. RESULTS: Horses with cervical compression had decreased beta-globulin fraction, and 1 or 2 prominent post-beta 2 peak(s). When the presence of post-beta peaks was used as a diagnostic criterion for cervical compression, the test had sensitivity of 71.4% and specificity of 81.8%. The positive and negative predictive values were 83.3 and 69.2%, respectively. CONCLUSION AND CLINICAL IMPLICATIONS: Electrophoresis of CSF may be a useful diagnostic aid in evaluation of horses with neurologic disease.

Animals↗
PubMed1997

Acrylamide and 2,5-hexanedione induce collapse of neurofilaments in SH-SY5Y human neuroblastoma cells to form perikaryal inclusion bodies.

Neurofilament accumulations are characteristic of a number of neurological conditions including amyotrophic lateral sclerosis, giant axonal neuropathies and several chemically-induced neuropathies. Although the mechanism(s) leading to neurofilament accumulation are unknown, it is possible that similar processes occur both in disease and in chemically-induced neuropathies. Understanding the mechanism(s) of chemically-induced neurofilament accumulation, which is more amenable to experimental manipulation, may give insight into the neurological diseases they mimic. We have compared the effects of two chemically-dissimilar neurotoxins, 2,5-hexanedione and acrylamide, on neurofilaments in the human neuroblastoma cell line, SH-SY5Y. Both undifferentiated and differentiated SH-SY5Y cells were exposed to 2,5-hexanedione or acrylamide and changes in cytoskeletal organization examined by immunofluorescence and electron microscopy. Although distinct morphological differences have previously been characterized in the neuropathies induced by 2,5-hexanedione and acrylamide in vivo, we have found that both compounds had similar direct effects on neurofilaments in SH-SY5Y cells, inducing formation of perikaryal inclusion bodies. In addition, differentiated SH-SY5Y cells were more sensitive to both 2,5-hexanedione and acrylamide compared with undifferentiated cells. These similar effects of 2,5-hexanedione and acrylamide lend further support that a common mechanism(s) may lead to neurofilament accumulation in these neuropathies. SH-SY5Y cells provide a useful model to investigate further the biochemical basis of neurofilament accumulation.

Acrylamide↗
PubMed1996

Influenza viruses display high-affinity binding to human polyglycosylceramides represented on a solid-phase assay surface.

Polyglycosylceramides (PGCs), complex glycolipids containing up to 50 or more sugar residues, are recognized as the minor components of the cell-surface membranes, but a knowledge on their tissue distribution, structure, and function is limited. In this study, the binding of influenza viruses to preparations of PGCs was investigated using a TLC overlay assay and a microwell adsorption assay. The ability of PGCs to bind influenza virus was dependent on the source from which they were derived. Preparations of PGCs from human erythrocytes were found to support binding of A and B influenza virus strains at a much lower concentration than sialyl-6-paragloboside and to be somewhat better receptors for these viruses compared to the sialylglycoprotein fetuin. A high virus-binding activity of PGCs suggests that these species could potentially serve as biologically important cell-surface receptors for influenza viruses.

Adsorption↗