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Biomedical subjects

M A Nelson

Publications and source records attributed to M A Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers.

A biomarker of skin cancer would be beneficial in evaluating the efficacy of potential cancer chemoprevention agents. To this end, we investigated the tumor suppressor gene p53 in precancerous actinic keratosis lesions (AK) and malignant squamous cell carcinomas (SCCs) using polymerase chain reaction and single-strand conformation polymorphism analysis (PCR-SSCP) techniques. In addition, p53 protein expression was evaluated using immunohistochemistical analysis with the PAB 1801 monoclonal antibody. Nine out of 13 (69%) SCCs and 8 of 15 (53%) AKs were positive for p53 mutations. In contrast, normal skin samples were negative for p53 mutations. Sequence analysis of AKs and SCCs showed primarily C to T transition mutations. Nuclear immunochemical staining for p53 was observed in 12/15 (80%) AK and 12/13 (92%) SSCs. These results suggest that p53 mutations may be involved in the malignant conversion of AKs to SCCs and that p53 may be useful as a biomarker to study the potential modulatory effects of cancer chemopreventive agents against skin cancer.

Base Sequence↗
PubMed1994

Establishment of a new lung sarcoma cell line from a human lung carcinosarcoma.

A cell-line (UACC 2561), was established from a biopsy specimen of a lung carcinosarcoma. The patient had Stage III non-small cell lung cancer. Characterization of this cell line revealed highly aneuploid cells containing multiple clonal chromosome alterations with growth in nude mice within 3 weeks following subcutaneous injection. The cell line UACC 2561 stained positive for vimentin and displayed resistance to a variety of chemotherapeutic agents. Polymerase chain reaction followed by single-strand conformational polymorphism analysis revealed the presence of a K-ras 12 codon mutation. This mutation was confirmed by mutation specific PCR analysis for mutant K-ras alleles and direct DNA sequencing to be a GGT to GTT at codon 12 of the K-ras gene. Examination by PCR-SSCP for p53 mutations did not reveal any point mutations in exon 5-8 of the p53 gene. This relatively rare cell line may represent a useful model to investigate human lung sarcomas.

Animals↗
PubMed1994

Economic impoverishment as a health risk: methodologic and conceptual issues.

Although economic impoverishment has long been recognized as a health risk, it has not generally been targeted as a modifiable risk factor. A number of methodologic and conceptual issues have impeded and obscured explanation of the nature and characteristics of the relationship between socioeconomic status and health. Further investigation is needed to address directional effects, confounding factors, and measurement difficulties. Conceptual representations of the links between economic impoverishment and health need to be clarified and expanded. Until this relationship is better understood, development of effective strategies to improve health for the economically disadvantaged will be problematic.

Confounding Factors, Epidemiologic↗
PubMed1994

The fate of inflorescence meristems is controlled by developing fruits in Arabidopsis.

The relationship between fruit development and the proliferative capacities of inflorescence meristems has been examined in Arabidopsis thaliana. In the wild-type Landsberg erecta (Ler) line, flower production ceases coordinately on all inflorescence branches by a process we have designated global proliferative arrest (GPA). Morphological studies indicate that GPA involves a cessation of proliferative activity at the meristems, but a retention of the structural characteristics of the proliferating meristems. GPA does not occur in the male-sterile (ms1-1) line, nor in wild-type Ler when fruits are surgically removed. In these cases, inflorescence meristems continue to proliferate, ultimately terminating by a different process, designated terminal differentiation, in which disruptions in patterning at the apex are followed by the loss of the inflorescence meristem. We present an argument that GPA is mediated by a specific communication system between inflorescence meristems and developing fruits. Analysis of reduced-fertility mutants provided evidence that GPA is dependent on seed development specifically. Mutations conferring hormone deficiency or insensitivity did not disrupt the correlative interactions leading to GPA.

Arabidopsis↗
PubMed1993

Race, gender, and the effect of social supports on the use of health services by elderly individuals.

This study examines the effects of social supports on the use of health services by elderly individuals, and whether those effects differ by race or gender. Multiple regression analysis of the 5,151 baseline Longitudinal Study on Aging (LSOA) respondents revealed that social supports, mainly church attendance, increased the R2s when estimated separately within race and gender groups in a statistically significant manner. The magnitude of these increases, however, was small suggesting that their unique contribution may be minimal. The effects of the social support variables on the use of health services differed by race and gender. These differences, however, were not consistent across the various measures of health services utilization.

Activities of Daily Living↗
PubMed1992

Analysis of the Harvey ras gene in cisplatin-initiated mouse skin tumors by polymerase chain reaction and direct DNA sequencing.

Cisplatin (cis-dichlorodiammineplatinum (II)) acts as a tumor initiator in the mouse skin model of carcinogenesis. DNA transfection studies suggested that skin tumors initiated by cisplatin contained dominant transforming activity. Since the Harvey-ras (H-ras) gene is known to be activated by point mutations in chemically initiated mouse skin tumors, we used polymerase chain reaction (PCR) and direct DNA sequencing to analyze the DNA sequence of the H-ras gene in twelve different cisplatin-initiated skin tumors. The results of these studies indicated that cisplatin-initiated skin tumors were normal (wild-type) at codons 12, 13, 61 and 117. Thus the transforming activity associated with cisplatin initiated mouse skin tumors was not due to a mutant H-ras gene and this suggests the involvement of other transforming genes during initiation of the mouse skin with cisplatin.

Animals↗
PubMed1992

Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis before the development of benign tumors.

An activated Ha-ras oncogene has been consistently found in chemically initiated benign and malignant mouse skin tumors, and an activated ras oncogene has been shown to initiate the process of mouse skin carcinogenesis. However, the exact timing of mutational activation of the Ha-ras gene relative to application of the chemical carcinogen is not known. A sensitive mutation-specific PCR technique was used to experimentally address the timing of Ha-ras gene mutational activation. This technique can detect mutant Ha-ras alleles in the presence of a very large excess of normal ras alleles. Activated Ha-ras genes with 61st codon A----T mutations were found in the epidermis of mice 1 week after topical initiation with 7,12-dimethylbenz[a]anthracene or urethane by using this assay. These results were confirmed by Xba I restriction fragment length polymorphism analysis and direct DNA sequencing. One week after initiation is 1-2 months before the appearance of benign papillomas that harbor activated Ha-ras oncogenes when the initiated mice are promoted with the tumor promoter phorbol 12-myristate 13-acetate. Our data support the hypothesis that initiated epidermal cells containing an activated Ha-ras gene can remain dormant in the skin until a tumor promoter induces regenerative hyperplasia that allows for outgrowth of these cells with an activated ras oncogene to give rise to a benign papilloma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Sexual development genes of Neurospora crassa.

The filamentous fungus Neurospora crassa undergoes a complex program of sexual development to form a fruiting body composed of several kinds of specialized tissue. Subtractive hybridization was used to isolate genes that are expressed preferentially during this sexual phase. Many such sexual development (sdv) genes were identified in a cosmid library of Neurospora genomic DNA. Fourteen of the sdv genes were subcloned, and their expression in mutant strains and under crossing and vegetative growth conditions was examined. All of the regulated transcripts were less abundant (and in many cases not detectable) in strains grown under vegetative (high nitrogen) conditions, suggesting that nitrogen starvation is required for their synthesis. The expression of most of the sdv genes also required a functional A mating type product, even under crossing growth conditions, suggesting that this product functions as a master control in sexual development. To determine if the products of the sdv genes play essential roles in the sexual cycle, a reverse-genetic approach (based on RIP (repeat-induced point mutation)-mediated gene disruptions) was used to create mutations in the genes. A mutant strain (asd-1) with a recessive crossing defect (apparently caused by the RIP process) was isolated; in this strain, early development is normal and may asci are formed, but ascospores are never delineated. A second recessive mutant strain (asd-2) was apparently created by ectopic integration of the transforming DNA into a gene required for the sexual process; in this strain the sexual process was blocked at an early stage, and the ascogeneous tissue underwent little development.

Cell Differentiation↗
PubMed1990

Increased expression of c-myc and c-Ha-ras in dichloroacetate and trichloroacetate-induced liver tumors in B6C3F1 mice.

The expression of c-myc and c-H-ras in hyperplastic nodules and hepatocellular carcinomas induced in male B6C3F1 mice after chronic administration of dichloroacetate (DCA) and trichloroacetate (TCA) was studied using in situ hybridization. Expression of c-myc and c-H-ras mRNA was increased in both nodules and carcinomas relative to surrounding tissue and tissues obtained from control animals. Myc expression was similar in hyperplastic nodules and carcinomas induced by DCA, but was significantly higher in TCA-induced carcinomas than in hyperplastic nodules and carcinomas produced by DCA. In carcinomas from animals whose TCA treatment was suspended at 37 weeks, c-myc expression remained high relative to control and surrounding liver tissue at 52 weeks. In contrast, the expression of c-H-ras was consistently elevated in carcinomas from both treatments relative to hyperplastic nodules and non-tumor tissue. Within carcinomas from both treatments, focal areas could be located which expressed even higher levels of c-myc. This heterogeneity was not observed in carcinomas hybridized to c-H-ras-probes. These data suggest that elevated expression of c-H-ras and c-myc might play an important role in the development of hepatic tumors in B6C3F1 mice. Elevated expression of c-H-ras was closely associated with malignancy. Increased c-myc expression does not seem necessary for progression to the malignant state. On the other hand, the increased expression of c-myc appears related to the earlier progression of TCA-induced tumors to the malignant state.

Animals↗
PubMed1990

Liver tumor induction in B6C3F1 mice by dichloroacetate and trichloroacetate.

Male and female B6C3F1 mice were administered dichloroacetate (DCA) and trichloroacetate (TCA) in their drinking water at concentrations of 1 or 2 g/l for up to 52 weeks. Both compounds induced hepatoproliferative lesions (HPL) in male mice, including hepatocellular nodules, adenomas and hepatocellular carcinomas within 12 months. The induction of HPL by TCA was linear with dose. In contrast, the response to DCA increased sharply with the increase in concentration from 1 to 2 g/l. Suspension of DCA treatment at 37 weeks resulted in the same number of HPL at 52 weeks that would have been predicted on the basis of the total dose administered. However, none of the lesions in this treatment group progressed to hepatocellular carcinomas. Conversely, the yield of HPL at 52 weeks when TCA treatment was suspended at 37 weeks was significantly below that which would have been predicted by the total dose administered. In this case, 3 of 5 remaining lesions were hepatocellular carcinomas. Throughout active treatment DCA-treated mice displayed greatly enlarged livers characterized by a marked cytomegaly and massive accumulations of glycogen in hepatocytes throughout the liver. Areas of focal necrosis were seen throughout the liver. TCA produced small increases in cell size and much a more modest accumulation of glycogen. Focal necrotic damage did not occur in TCA-treated animals. TCA produced marked accumulations of lipofuscin in the liver. Lipofuscin accumulation was less marked with DCA. These data confirm earlier observations that DCA and TCA are capable of inducing hepatic tumors in B6C3F1 mice and argue that the mechanisms involved in tumor induction differ substantially between these two similar compounds. Tumorigenesis by DCA may depend largely on stimulation of cell division secondary to hepatotoxic damage. On the other hand, TCA appears to increase lipid peroxidation, suggesting that production of radicals may be responsible for its effects.

Animals↗
PubMed1989

Dichloroacetic acid and trichloroacetic acid-induced DNA strand breaks are independent of peroxisome proliferation.

This study examined whether the induction of single strand breaks in hepatic DNA by dichloroacetic acid (DCA) and trichloroacetic acid (TCA) depends upon peroxisome proliferation. Male B6C3F1 mice were given a single oral dose of either DCA or TCA. At varying times, between 1 and 24 h after administration of the compounds, breaks in DNA were measured using an alkaline unwinding assay. Peroxisome proliferation was monitored at the same time intervals in a parallel experiment by measuring peroxisomal B-oxidation of [14C]palmitoyl-CoA in liver homogenates. Both DCA and TCA significantly increased breaks in DNA at 1, 2, and 4 h post-treatment, with a return to control levels after 8 h. No evidence for an increase in peroxisomal beta-oxidation was produced by either chemical up to 24 h after administration. In a separate experiment, mice were treated with DCA or TCA for 10 days and their livers examined for evidence of peroxisome proliferation. An increase in liver weight was observed, particularly with DCA. Both TCA and DCA increased peroxisomal beta-oxidation in liver homogenates, with TCA-treated animals showing more activity than those treated with DCA. Electron microscopy revealed that the number of peroxisomes were approximately the same in DCA- and TCA-treated animals. However, peroxisomes induced by DCA treatment frequently lacked nucleoid cores. These data indicate that peroxisomes induced by these compounds differ in their concentration of peroxisomal enzymes. Except for a slight hypertrophy, repeated doses of TCA do not produce significant degenerative changes in the liver of mice. Repeated doses of DCA produce multifocal, subcapsular necrotic regions, and a marked hypertrophic response in the liver. Mice treated with TCA for 10 days and sacrificed 24 h after the last dose did not display increased strand breaks in hepatic DNA. This indicates that peroxisomal proliferation does not contribute to the induction of DNA strand breaks.

Acetates↗
PubMed1989

Partial attenuation of hemodynamic responses to rapid sequence induction and intubation with labetalol.

The effectiveness of labetalol (a combination nonselective beta and alpha-1-adrenergic receptor antagonist) in modifying hemodynamic responses associated with rapid sequence induction and tracheal intubation was evaluated. In a double-blind study, 24 ASA physical status I or II male patients scheduled for elective surgery were given either IV labetalol, 0.25 mg/kg (n = 8) or 0.75 mg/kg (n = 8), or a saline placebo (n = 8). Five minutes later, patients were given oxygen by mask and IV vecuronium, 0.01 mg/kg. Ten minutes after giving labetalol or placebo, cricoid pressure was applied and anesthesia was induced with IV sodium thiopental (4 mg/kg) and succinylcholine (1.5 mg/kg) 1 minute prior to intubation. The mean duration of laryngoscopy was 17 +/- 3 seconds. Prior to induction, the 0.25 mg/kg and 0.75 mg/kg doses of labetalol significantly (p less than 0.05) reduced mean arterial pressure by 4.4 +/- 1.9 and by 8.6 +/- 2.0 mmHg, respectively, but did not significantly alter heart rate or cardiac output. The 0.75 mg/kg dose of labetalol also significantly (p less than 0.05) decreased total peripheral resistance by 10.1 +/- 3.0%. Within 30 seconds after intubation, patients in all three groups exhibited increases in heart rate, mean arterial pressure, total peripheral resistance, and rate pressure product and a decrease in stroke volume. However, patients in the 0.25 and 0.75 mg/kg labetalol groups, compared to those in the placebo group, had significantly lower increases in peak heart rate (33 +/- 2 and 27 +/- 3 vs. 44 +/- 7 beats/minute), peak mean arterial pressure (38 +/- 6 and 38 +/- 7 vs. 58 +/- 7 mmHg), and peak rate pressure product (7,726 +/- 260 and 7,215 +/- 300 vs. 14,023 +/- 250 units). The results show that these doses of labetalol significantly blunt, but do not completely block, autonomic responses to rapid sequence induction and intubation.

Adult↗
PubMed1989

Public policy, local labor demand, and migration in Sweden, 1979-84.

"A model of private local labor demand and interjurisdictional migration is presented and estimated using data from Swedish counties and municipalities for 1979-84. Our goal is to compare the effects on local labor markets of distinctive public-sector programs with those of traditional market variables. We find that local income taxes and tax-equalization grants have important effects on local labor markets; regional development policy measures and geographical-mobility subsidies do not. Thus, recent efforts scaling back some of these programs may not materially alter the regional economy's performance. Wages and other traditional market variables are also often found to influence significantly local labor markets."

Demography↗
PubMed1989

Molecular cloning of a Neurospora crassa carotenoid biosynthetic gene (albino-3) regulated by blue light and the products of the white collar genes.

The albino-3 (al-3) gene of Neurospora crassa, which probably encodes the carotenoid biosynthetic enzyme geranylgeranyl pyrophosphate synthetase, was cloned. The N. crassa triple mutant al-3 qa-2 aro-9 was transformed to qa-2+ with mixtures of plasmids bearing N. crassa DNA inserts, and the transformants were screened for the al-3+ phenotype. One al-3+ qa-2+ transformant (AL3-1) was examined in detail and shown to contain intact vector sequences integrated into the N. crassa genome. The vector and some flanking sequences were recovered from AL3-1 after restriction, ligation, and selection of chloramphenicol-resistant transformants of Escherichia coli. The flanking sequences were subsequently used to detect the al-3-containing plasmid in the mixture of about 1,800 plasmids. Restriction fragment length polymorphism mapping was carried out to confirm the identity of the cloned fragment. The level of the al-3 mRNA was shown to be increased 15-fold in light-induced (compared with that in dark-grown) wild-type mycelia. The light-dependent increase in al-3 mRNA levels was not observed in presumed regulatory mutant (white collar) strains.

Carotenoids↗