Biomedical subjects

J Paterson

Publications and source records attributed to J Paterson.

At least 19 recordsLinked to original sources

PubMed1995

Elevated DNA repair capacity is associated with intrinsic resistance of lung cancer to chemotherapy.

Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA repair in intrinsic resistance of N-SCLC to cisplatin. A panel of primary N-SCLC cell cultures and established cell lines were examined and compared to SCLC cell lines established previously from untreated patients. The overall DNA repair capacity was estimated by the ability of cells to reactivate the pRSV-CAT plasmid damaged by cisplatin ("host cell reactivation" assay). Cytotoxicity was determined for cisplatin in vitro. N-SCLC cells were found to be significantly more resistant to cisplatin than SCLC cell lines isolated from untreated patients (P < 0.01). The capacity of N-SCLC cells to reactivate pRSV-CAT plasmid damaged with cisplatin and transfected into cells was higher in N-SCLC cells than in SCLC cells originating from patients who were untreated previously (P < 0.05). Correlation was also observed between chloramphenicol acetyltransferase activity and intrinsic resistance to cisplatin. However, no significant difference was observed between primary N-SCLC cultures and established cell lines. This study indicates that elevated DNA repair capacity is associated with drug resistance in lung cancer and suggests that modulation of DNA repair mechanism(s), such as the incorporation of specific DNA repair inhibitor(s) in therapeutic regimens, may help to improve therapeutic strategies of N-SCLC.

Aged↗

PubMed1995

The effects of fescue toxicosis on beef cattle productivity.

Consumption of tall fescue forage infested with the endophytic fungus Acremonium coenophialum can result in a condition termed "fescue toxicosis," which is characterized by decreased weight gains, milk production, conception, and serum prolactin and an inability to dissipate body heat by beef cattle. These decreases in productivity have been estimated to cost beef producers more than $600 million annually. The unthrifty appearance of cattle consuming endophyte-infected tall fescue (E+) is most evident during periods of environmental heat or cold stress, suggesting an interaction with environmental conditions. Without temperature stress, cows consumed similar amounts of E+ and endophyte-free tall fescue (E-). But, when temperatures exceeded 32 degrees C, cows that grazed E+ consumed less forage than cows that grazed E-. After removal of E+ from the diet of steers, compensatory growth was observed, indicating no long-term negative effects of E+. A decrease in serum prolactin but apparently little change in other hormones has been measured after consumption of E+. Under periods of heat stress, animals had reduced ability to dissipate body heat, and blood flow to peripheral (rib skin), core-body (duodenum colon), and brain (cerebellum) tissues was decreased. Due to the depressive effects of E+ on prolactin and heat dissipation, dopamine antagonist therapy has been used in an attempt to rectify these changes. Dopamine antagonists have increased serum prolactin but there is limited evidence to suggest an improvement in heat dissipation. Experiments to elucidate the effects of E+ on alpha-1 and -2 adrenergic receptors may also offer insights into developing strategies to overcome the negative effects of E+ consumption. Preliminary results suggest that injections of an alpha-1 adrenergic antagonist (prazosin) in rats fed E+ under 32 degrees C conditions increased DM intake and reduced rectal temperature.

Acremonium↗

PubMed1995

Differentiation and tumor response to retinobenzoic acid RE-80 in a malignant conversion model.

The synthetic retinobenzoic acid RE-80 was evaluated for its potential as an inductor of tumor cell differentiation and as a chemopreventive agent. A minimally toxic dose of RE-80 in vitro produced morphologic changes typical differentiation in epidermal tumor cell colonies. Indirect immunofluorescence indicated induction of a differentiation-associated keratin of internal stratified epithelia, K13, and inhibition of the differentiation-associated epidermal keratin K1. Cultured cells were skin-grafted to athymic nu/nu mice to evaluate RE-80 effects on early stage malignant progression in vivo. When tumors had grown to 3 to 4 mm in diameter, mice were treated by intraperitoneal injection with RE-80 (67 micrograms, 170 mmol, i.p., two times per week) or vehicle (100 microliters 20% ethanol). Papillomas (benign) and moderately differentiated squamous cell carcinomas were reduced in volume about 4-fold by RE-80 treatment. Larger, poorly differentiated squamous cell carcinomas were unaffected. RE-80 resulted in a lower proportion of proliferative cells (detectable by bromodeoxyuridine incorporation) and a higher proportion of moderately to well differentiated tumors after 40 days of treatment compared with control tumors, which were mainly poorly differentiated squamous cell carcinomas. K13 induction in vitro was correlated with response to retinoid in vivo. Induction of differentiation may be mechanism of the response to RE-80 in vivo since carcinoma cells expressing K13 did not incorporate bromodeoxyuridine and were on a terminal pathway.

Animals↗

PubMed1995

New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome.

The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function.

Abnormalities, Multiple↗

PubMed1994

X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene.

X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes from part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.

Aphasia↗

PubMed1993

AIDS-related knowledge, fear, and behavioral change among nurses in Taiwan.

Current literature documents a phenomenon of fear that affects the willingness of health care professionals to care for persons with acquired immunodeficiency syndrome (AIDS). We attempted to identify differences between nurses who exhibit fearful attitudes toward AIDS and those who do not, based on knowledge and behavior. Taiwan, site of the study, is only beginning to identify the first of its citizens with AIDS. The subjects were a population of caregivers from a culture with little exposure, therefore, either through education or experience, to the disease and the issues it engenders. A cross-sectional, self-administered survey was conducted in 1990 of 1759 nurses in 12 institutions throughout Taiwan. Data on AIDS-related knowledge, fear, and behavior, as well as selected demographic data, were gathered. Analysis revealed significantly less fear of AIDS among nurses who reported three behavioral changes related to AIDS than among those who reported fewer changed behaviors (F = 4.43, df = 3; P < 0.004); those with higher levels of education (F = 3.54, df = 3; P < 0.014); and those who were single rather than married (t = 2.81; P < 0.005).

Acquired Immunodeficiency Syndrome↗

PubMed1993

Refining the genetic location of the gene for X linked hydrocephalus within Xq28.

The most common inherited form of hydrocephalus, X linked hydrocephalus (HSAS), is characterised by mental retardation, adducted thumbs, and spastic paraplegia. Genetic analysis has mapped the locus for HSAS to subchromosomal band Xq28 within a region of approximately 2 megabases of DNA. In order to refine the location of the disease gene we have conducted genetic linkage analysis with Xq28 marker loci in four additional HSAS families. A lod score of 4.26 with polymorphic marker DXS52 (St14) confirms the linkage of HSAS to Xq28. Identification of a recombination event between the HSAS gene and Xq28 loci F8C and DXS605 (2-19) reduces the size of the interval likely to contain the disease locus to about 1.5 megabases, the distance between DXS605 and DXS52. The locus for neural cell adhesion molecule, L1CAM, maps within this interval and therefore represents a candidate gene for HSAS.

Adolescent↗

PubMed1991

Structure and transcription of the singed locus of Drosophila melanogaster.

Developmental and genetic studies of the singed gene of Drosophila melanogaster indicate that the gene has a role in somatic cells during the formation of adult bristles and hairs, and in the female germline during oogenesis. During metamorphosis a single 3.6-kilobase (kb) RNA is made, and this RNA is also present in adults and early embryos. Early embryos and adult females have additional 3.3- and 3.0-kb RNAs. The RNAs differ only in the length of the 3' untranslated region and a single gene product of 57 kilodaltons is predicted. Analysis of RNA from females lacking ovaries suggests that the 3.3- and 3.0-kb RNAs are made only in ovaries. The absence of the 3.3- and 3.0-kb RNAs in pupae and the time course of their appearance in adult females after eclosion suggests that transcription of singed in the ovary is from middle to late stages of oogenesis. Analysis of RNA in embryos from the reciprocal crosses between wild type and singed-3 showed that all three RNAs are maternally inherited with very little zygotic transcription in embryos. The mutation singed-3 appears to separate the two requirements for singed function as it has an extreme effect upon bristle development, but does not obviously affect oogenesis. In singed-3, there is a deletion at the 5' end of the gene, but the coding region is intact. Transcription in singed-3 is from a cryptic promoter in the upstream flanking sequences which is sufficiently active during oogenesis for fertility, but less active than the wild-type promoter during metamorphosis. The role of the single singed gene product may be in the asymmetric organization and/or movement of cytoplasmic components.

Amino Acid Sequence↗

PubMed1990

Plasma levels of morphine and morphine glucuronides in the treatment of cancer pain: relationship to renal function and route of administration.

There is growing evidence that renally-impaired patients receiving morphine therapy are at greater risk of developing opiate toxicity, due to the accumulation of an active metabolite, morphine-6-glucuronide (M6G), which is usually excreted by the kidneys. This study examined the relationships between morphine dosage, renal function, and trough plasma concentrations of morphine and its glucuronide metabolites in 21 patients (aged mean: 68.5 years: 11 males) receiving either oral or subcutaneous morphine for terminal cancer pain. The median daily morphine dosages (mg.kg-1) were: orally 1.87 (range 0.37-6.82) and subcutaneously 1.64 (range 0.22-3.60). The median plasma concentrations of morphine, morphine-3-glucuronide (M3G), and M6G (ng.ml-1) were: 36.0, 1035.2, and 142.3, respectively. The plasma concentrations of morphine, M3G and M6G were each significantly related to the daily morphine dosage (n = 21, Spearman r = 0.79, 0.91, and 0.88 respectively). Accumulation of the morphine glucuronides was dependent on renal function. The plasma concentrations of M3G and M6G, when divided by the morphine concentration, were significantly related to the calculated creatinine clearance of the patient. Patients receiving oral morphine had higher plasma concentration ratios of glucuronide/morphine than those receiving subcutaneous therapy, presumably due to first-pass glucuronidation. The results of this study confirm that accumulation of the pharmacologically active M6G is related to renal function, which probably explains the observation that morphine dosage requirements are generally reduced in patients with renal impairment.

Aged↗

PubMed1990

Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy.

This study examined dosage prescribing patterns and steady-state oxipurinol plasma concentrations in 66 patients receiving chronic allopurinol therapy. Most patients (65%) were taking 300 mg allopurinol daily, although renal impairment was common. Using published guidelines, it was estimated that 35% of patients were receiving excessive dosages of allopurinol. Consequently, the plasma oxipurinol concentrations were often very high (mean (SD) was 156 (109) mumol.l-1). Accumulation of oxipurinol was inversely related to renal function. Plasma concentrations of oxipurinol and urate were not significantly related. However, most patients with oxipurinol concentrations of up to 100 mumol.l-1 had urate concentrations within the normal reference range.

Aged↗

PubMed1989

Palliative care.

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Aged↗

PubMed1989

Cholecystokinin concentration in specific brain areas of rats fed during the light or dark phase of the circadian cycle.

Measurement of peptide concentration in specific areas can be used as an initial investigative method for identifying brain sites in which the peptides may be acting. In this study cholecystokinin (CCK) concentration in specific hypothalamic and hindbrain areas of male Sprague-Dawley rats was measured in order to determine whether changes occurred as a result of feeding activity during different portions of the circadian cycle. Three groups of 40 rats each were studied: Group 1 were fasted 16 hr during the dark phase then sacrificed immediately or after a 20 min light phase meal. Group 2 were fasted 16 hr during the light phase then sacrificed immediately after lights out or after a 20 min dark-onset meal. Group 3 were fed ad lib and sacrificed immediately after light out or after a 20 min dark-onset meal. CCK was extracted from dissected areas and concentration was measured by RIA. There was no difference in CCK concentration of any of the 9 brain areas in rats fasted during the dark phase and fed during the light phase. In rats fasted during the light phase CCK concentration of the paraventricular nucleus (PVN) was greater in those that subsequently ate a meal at dark-onset than in those that did not eat (p less than 0.05). In ad lib fed rats CCK concentration was less in the anterior hypothalamus (AH) and greater in the supraoptic nucleus (SON) in rats that ate a dark-onset meal than in rats that did not (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Evaluation of the efficacy of trace element supplementation of an anthelmintic.

The efficacy of the selenium and cobalt contents of a trace element supplemented anthelmintic was evaluated in a series of trials with lambs in Scotland and Northern Ireland. The product was compared with other methods of supplementation and was found to be an adequate source of selenium when administered at monthly intervals. Its cobalt content was shown to be of some nutritional benefit on four of five sites but not as effective as the monthly 250 mg oral cobalt dose, vitamin B12 injection or intraruminal soluble glass bolus treatments also used. No growth responses were obtained and unsupplemented animals generally had an adequate cobalt and selenium status. No toxicity problems were encountered from either element.

Animals↗

PubMed1986