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L Garfinkel

Publications and source records attributed to L Garfinkel.

At least 37 records · Page 2Linked to original sources
PubMed1989

An artificial-intelligence technique for qualitatively deriving enzyme kinetic mechanisms from initial-velocity measurements and its application to hexokinase.

We have developed a computer method based on artificial-intelligence techniques for qualitatively analysing steady-state initial-velocity enzyme kinetic data. We have applied our system to experiments on hexokinase from a variety of sources: yeast, ascites and muscle. Our system accepts qualitative stylized descriptions of experimental data, infers constraints from the observed data behaviour and then compares the experimentally inferred constraints with corresponding theoretical model-based constraints. It is desirable to have large data sets which include the results of a variety of experiments. Human intervention is needed to interpret non-kinetic information, differences in conditions, etc. Different strategies were used by the several experimenters whose data was studied to formulate mechanisms for their enzyme preparations, including different methods (product inhibitors or alternate substrates), different experimental protocols (monitoring enzyme activity differently), or different experimental conditions (temperature, pH or ionic strength). The different ordered and rapid-equilibrium mechanisms proposed by these experimenters were generally consistent with their data. On comparing the constraints derived from the several experimental data sets, they are found to be in much less disagreement than the mechanisms published, and some of the disagreement can be ascribed to different experimental conditions (especially ionic strength).

Adenosine Triphosphate↗
PubMed1989

Histologic changes in the urinary bladder in relation to cigarette smoking and use of artificial sweeteners.

A total of 6503 sections of urinary bladder epithelium from 282 subjects were examined in random order, and histologic alterations, particularly the number of cell rows and the presence and extent of cells with atypical nuclei, were recorded. Cases were either individuals who had never smoked or who had smoked cigarettes. Microscopic slides with cells having 50% or more atypical nuclei were found in 4.3% of those who had never smoked; 67.1% in those who had smoked less than 20 cigarettes a day; 82.3% in those who had smoked 20 to 39 cigarettes a day; and 88.4% of the 40 or more a day cigarette smokers. The percentage of slides with six or more cell rows in these groups were 4.8%, 52.2%, 62.5%, and 72.9%, respectively. The histologic findings in the urinary bladder in relation to smoking habits fully complement the epidemiologic studies showing a dose-response of cigarette smoking and urinary bladder cancer. No relationship was found between changes in the urinary bladder epithelium and the use of artificial sweeteners.

Adolescent↗
PubMed1989

A case-control study of multiple myeloma nested in the American Cancer Society prospective study.

Among the subjects enrolled in the American Cancer Society Cancer Prevention Study II, a large nation-wide prospective study, 282 died from multiple myeloma (MM) during the first 4 years of follow-up. These were divided into incident cases who were initially free from disease and prevalent cases who reported MM or related symptoms at the time of enrollment. For each case, 4 controls matched for age, sex, ethnic group and residence were randomly selected. Previous history of diabetes [odds ratio (OR) = 2.0] and employment as farmer (OR = 2.7) were the risk factors consistently suggested by the results of the analysis. The risk associated with farming showed a linear trend with duration of exposure. Pesticide or herbicide exposure was not a risk factor per se but, when combined with farming, it increased the OR to 4.3. Low education, occupational exposure to dyes, and employment in a bank, on the railroad or as a maid were also suggested risk factors, but either they were not statistically significant or they were based on small numbers of exposed subjects. No association between MM and asbestos exposure was observed.

Adult↗
PubMed1989

Entamoeba histolytica ribosomal RNA genes are carried on palindromic circular DNA molecules.

Highly abundant DNA fragments obtained after restriction enzyme digests of nuclear DNA of Entamoeba histolytica strain HM-1:IMSS have been cloned and characterized. Northern blot hybridization to E. histolytica rRNA and sequence analysis identified the abundant DNAs as ribosomal DNA containing species. Several overlapping clones containing these abundant DNAs were isolated from 4 different genomic libraries of E. histolytica. Alignment of the restriction maps was consistent with a circular molecule, about 24.6 kilobase pairs (kb) in size. Nuclease BA131 digestion provided additional evidence for the circular nature of this DNA. The ribosomal DNA molecule contains two large inverted repeat-regions, each at least 5.2 kb in length. Sequence analysis of clone R715 revealed homology to the large rRNA units of various eukaryotic organisms. This clone was located in both inverted repeats, suggesting two rRNA cistrons per molecule. The inverted repeats are flanked by stretches of DNA which contain tandemly reiterated sequences. Southern blot analysis of E. histolytica nuclear DNA revealed the presence of two populations of molecules. These molecules have identical arrangements of restriction sites, but differ in size (0.7 kb) in a fragment containing tandemly reiterated sequences. Analysis of E. histolytica nuclear DNA by electron microscopy also revealed circular molecules. These molecules are about 26.6 kb +/- 0.5 kb in size and contain structural features predicted by the restriction map of the extrachromosomal ribosomal DNA of E. histolytica.

Animals↗
PubMed1989

Lung cancer risk is proportional to cigarette tar yield: evidence from a prospective study.

The age-adjusted risk for lung cancer among over 120,000 male current cigarette smokers in the American Cancer Society's 1959-1972 prospective study was analyzed according to tar yield and quantity smoked per day. At each quantity level, the risk increased with increasing tar yield, and at each tar level, the risk increased with numbers of cigarettes smoked daily. The risks in smokers of cigarettes with the lowest yields, however, far exceeded those of former smokers and nonsmokers. The excess lung cancer risk for current smokers was directly proportional to the estimated total milligrams of tar consumed daily: SMR = 100 + 1.731 x milligrams tar per day. Tar yields today are much lower than they were at the time of this study and presage an eventual reduction (but not elimination) of lung cancer risk for those who continue to smoke cigarettes, especially among lifetime smokers of low-tar cigarettes.

Humans↗
PubMed1989

Proportions of cancer deaths attributable to cigarette smoking in women.

Over two-thirds of a million American women mostly over age 45 were enrolled in a prospective mortality study in 1982 and followed up for four years. In this time period 1,527 women died of six smoking-related cancer sites: oral cavity, esophagus, pancreas, larynx, lung, and bladder. Age-adjusted death rates in nonsmokers were used to obtain smoking-attributable risks and numbers of deaths due to these six cancers. Among current smokers, 601 deaths (85.5% of current smokers' deaths) were attributable to cigarette smoking, and among former smokers 284 (69.3% of ex-smokers' deaths) were attributable to smoking. Cigarette smoking accounted for 885 excess deaths at these sites, giving a population-attributable risk of 57.9%. Over three-quarters of these excess deaths were due to lung cancer. Cigarette smoking, despite increases in smoking cessation, is still responsible for well over half of the deaths from these six types of cancer in women.

Adult↗
PubMed1988

Smoking and lung cancer in women: findings in a prospective study.

Lung cancer rates in relation to smoking habits were studied in a cohort of 619,225 women traced over a 4-yr period (1982 to 1986). A total of 1,006 lung cancer deaths was recorded. The standardized mortality ratio (SMR) for women smokers was 12.7 for current smokers and 4.8 for exsmokers. For those women without a history of chronic diseases, the SMR rose to 17.6 for current smokers. The SMRs rose with the number of cigarettes smoked per day to 22.0 for women who smoked 31 or more per day. SMRs also increased with depth of inhalation; this increase was independent of the number smoked per day. SMRs also increased by duration of smoking and decreased with cessation of smoking. Mortality ratios for lung cancer in women ranged from about 2 to 1 to 3 to 1 in studies carried out in the 1950s and 1960s. As women have begun to smoke earlier in life, smoke more cigarettes a day, and inhale more deeply, we are now observing much higher SMRs in women with lung cancer, similar in magnitude to those seen in men in the earlier studies.

Adult↗
PubMed1988

Mortality by relative weight and exercise.

Mortality in relation to relative weight and exercise was analyzed from data collected in the first 2 years of the American Cancer Society's Cancer Prevention Study II. It included data on 868,620 persons who had no history of cancer, heart disease, or stroke and who were not sick at the start of the study. Standardized mortality ratios (SMR) were 187 for men who were 20% or more underweight and 187 for men who were 40% or more overweight. Comparable SMR in women were 186 and 178. Current smokers had considerably higher SMR than nonsmokers for all causes of death and cancer deaths at each relative weight category. Degree of exercise reported by subjects was inversely related to mortality, independent of smoking habits. Subjects who exercised heavily and died of cancer of the lung, colon-rectum, and pancreas had 20% to 37% higher SMR than men and women who reported moderate exercise.

Adult↗
PubMed1988

Smoking habits of 800,000 American men and women in relation to their occupations.

The distribution of cigarette smoking (as well as of cigar and pipe smoking in men) by occupation was examined in over 800,000 men and women age 45-70 who were enrolled in the American Cancer Society's prospective study in 1982. Striking variations were seen for men--less striking variations for women. Smoking rates were significantly higher in groups exposed to a number of occupational hazards, compared to groups not so exposed. A considerable amount of variation is related to social class, but some individual occupations exhibit notably high (law enforcement) or low (clergy) smoking rates. This information can be quite useful in planning morbidity or mortality studies of specific occupational groups or in analyzing data from existing studies.

Aged↗
PubMed1988

Diesel exhaust exposure and mortality among males in the American Cancer Society prospective study.

In 1982, the American Cancer Society enrolled over 1.2 million American men and women in a prospective mortality study of cancer and other causes in relation to different risk factors. The 2-year mortality of 461,981 males aged 40-79 years with known smoking habit has been analyzed in relation to exposure to diesel exhaust (DE) and to employment in selected occupations related to DE exposure. The relative risk (RR) for all causes of death for those exposed was 1.05 (95% confidence interval [CI]: 0.97-1.13). For lung cancer, the RR was 1.18 (95% CI: 0.97-1.44). A dose-response effect was present. Railroad workers, heavy equipment operators, miners, and truck drivers had a higher mortality both for all causes and for lung cancer when compared with subjects with other occupations and no exposure to DE. Truck drivers exposed to DE were not at excess risk of lung cancer if compared with truck drivers unexposed to DE, but a trend of increasing risk with duration of exposure was suggested. DE exposure was also associated with increase in mortality for accidents, cerebrovascular disease, arteriosclerosis, and cirrhosis of the liver. An association based on small numbers was also present for Hodgkin's disease and lymphoid leukemia. No association with chronic non-neoplastic pulmonary diseases or with bladder cancer was found.

Adult↗
PubMed1988

Theory formation in postulating enzyme kinetic mechanisms: reasoning with constraints.

This paper reports on a prototype system for modeling and analyzing the expert reasoning involved in postulating enzyme kinetic mechanisms. It involves data-driven, theory-driven, and analogical components of reasoning within a generate-and-test cycle. Its central component is a set of domain-specific "filters" for matching experimentally and theoretically derived constraints. The input to the system consists of an abstracted qualitative description of an experiment and prior knowledge reported in the literature. Its output shows how the results match those expected for a set of postulated reaction mechanism models and also provides a trace of which features do or do not match each of the candidate topological models. Results, constraints, and models are all analyzed and compared to those from other, similar experiments. We deduced rules for interpreting the qualitative features of enzyme kinetic experiments from natural language descriptions in the literature and verified that the rules were correct by predicting the results for typical mechanisms. We obtained the correct behavior for all 37 states of a complex enzyme mechanism involving three substrates and three products. We tested our system on data from several published reports dealing with the enzyme hexokinase and obtained detailed listings of the differences in conclusions and interpretation reported in several journal articles. This system, which provides qualitative representations of enzyme kinetic results, should facilitate further experimentation on theory formation in enzyme kinetics and lead to more efficient experimental designs.

Artificial Intelligence↗
PubMed1988

Alcohol and breast cancer: a cohort study.

The relation between alcohol consumption and several causes of death, including breast cancer, was examined in a population of 581, 321 women enrolled in a prospective study in 1959 and followed for 12 years. Women who drank occasionally had about the same breast cancer mortality rate as nondrinkers; those who drank one to four drinks per day had SMRs 7-26% higher; five drinks per day, 1.89; and six or more drinks per day, 1.65. The two highest-consumption groups' risks were significantly higher than those of nondrinkers after multivariate adjustment for several breast cancer risk factors. Distinctive dose-response relationships were observed for two known alcohol-related conditions: cirrhosis of the liver and cancer of the aero-digestive tract, suggesting that results for other causes are not seriously biased by misclassification of drinking habits. Death rates from all causes combined were elevated for drinkers of three or more drinks per day. Whether or not the association of elevated breast cancer death rates ultimately turns out to be causal, there is ample reason to continue to warn the public against excessive drinking.

Adult↗
PubMed1988

Nucleotide sequence analysis of an Entamoeba histolytica ferredoxin gene.

A cDNA clone (subclone B) previously isolated from the human parasite Entamoeba histolytica was characterized. DNA sequence analysis of subclone B identified the DNA as that encoding apoferredoxin. E. histolytica ferredoxin cDNA contains unusually short 5' and 3' noncoding regions of 9 and 25 nucleotides, respectively. A genomic ferredoxin clone was isolated from E. histolytica DNA, and comparison of genomic and cDNA sequences revealed that the ferredoxin gene is unspliced. The deduced amino acid sequence of E. histolytica ferredoxin resembles clostridial type of ferredoxins, and shows an arrangement of cysteines characteristic for the coordination of 2[4Fe-4S] centres. Of interest is the absence of an aromatic amino acid in the N-terminal region of the protein, a feature which is conserved in clostridial ferredoxins. Southern blot analysis of three different E. histolytica strains (200:NIH, Rahman and HM-1:IMSS) demonstrated the presence of a family of at least two ferredoxin genes. One of these genes is marked by restriction length polymorphisms in different strains of E. histolytica.

Amino Acid Sequence↗
PubMed1988

Magnesium and regulation of carbohydrate metabolism at the molecular level.

Enzymatic reactions involving the transfer of high-energy phosphate require a divalent metal ion as a participant. This is normally Mg2+ in biological situations, as its level within the cell is greater than other divalent metal ions. Although available methods for determining free cellular Mg2+ have thus far given divergent results, there is a growing body of evidence that its concentration is relatively low, approximately 0.5 mM. This low level permits control of important parts of carbohydrate metabolism, especially glycolysis, by Mg2+. The role of Mg2+ in regulating the phosphoryl-transfer enzymes of this pathway is described. Also described briefly is a series of computer models of this metabolism in heart and pancreatic islets. These models indicate considerable changes in Mg2+ level, and consequent control, especially when there are sharp changes in the glycolytic rate.

Carbohydrate Metabolism↗
PubMed1988

Patterns of artificial sweetener use and weight change in an American Cancer Society prospective study.

Extreme obesity and leanness are risk factors for many types of cancer. An earlier American Cancer Society study (1959-1972) found a nearly twofold increased risk for death from all causes in men and women who weighed 40% or more above average for their age and height, and found elevated cancer rates as well. A new (1982), ongoing ACS prospective study of 1.2 million men and women continues to find increased death rates from all causes and from cancer in the very heavy and the very lean. Artificial sweetener (AS) use is an important correlate of relative weight in this population. The relationship between weight change during the year preceding enrollment and AS usage was studied in a highly homogeneous subgroup of 78694 women ages 50-69 years. The percentage of users increased with body mass index (BMI) and was inversely related to age. Users were significantly more likely than non-users to gain weight, regardless of initial BMI. Among those who gained weight, the average number of lbs gained by AS users was higher (by 0.5-1.5 lb) than the amount gained by non-users. Within the entire cohort, AS users of both sexes ate chicken, fish and vegetables significantly more often than did non-users and consumed beef, butter, white bread, potatoes, ice cream and chocolate significantly less often, suggesting that our weight change results are not explicable by differences in food consumption patterns.

Aged↗
PubMed1987

Kinetic properties of hexokinase as assembled with a microcomputer data base.

We have constructed a relational data base containing the kinetic properties of the isoenzymes of hexokinase using the Knowledgeman data-base program on an IBM PC microcomputer. The natural subunit of this data base is the refereed publication, 165 of which were included. Reported values for the Mr (approx. 97,000) are in good agreement, but this agreement becomes progressively worse as one examines the Km values for glucose and ATP and the Ki for glucose 6-phosphate, where the reported values are spread over three orders of magnitude. Some quantities are very thinly or unreliably determined. Experimental conditions, especially free Mg2+ concentration, are rarely close to physiological. Reasons for the spread or uncertainty of numbers, and the distinctions that can be made between isoenzymes despite this spread, are discussed.

Adenosine Triphosphate↗
PubMed1987

Entamoeba histolytica: cloning and characterization of actin cDNA.

In order to study gene expression in the human parasite Entamoeba histolytica, a cDNA library of E. histolytica strain 200:NIH was constructed using the phage vector lambda gt10. Three cDNA clones (A, B and C) were selected for further analysis. Each of the three clones hybridized to a distinct mRNA. Two of these mRNAs were translated in vitro after hybrid selection, and yielded distinct translation products. One of these mRNAs, selected by hybridization to clone A, encodes the most abundantly expressed protein in E. histolytica. DNA sequence analysis of this cDNA clone identified the DNA as that encoding actin. The deduced amino acid sequence of E. histolytica actin resembles both cytoplasmic and muscle actins and has an unusual N-terminal glycine residue. We have shown that a family of actin genes is present in E. histolytica. Six different E. histolytica actin clones were obtained from a lambda gt10 genomic library using subcloned cDNA probes. Southern analysis of three different E. histolytica strains (200:NIH, Rhaman, and HM-1:IMSS) revealed at least four different actin genes. Strain HM-1:IMSS, however, differs by the presence of an additional actin gene.

Actins↗