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Biomedical subjects

L Garfinkel

Publications and source records attributed to L Garfinkel.

At least 55 records · Page 3Linked to original sources

Overweight and mortality.

Mortality ratios by relative weight categories compared to average weights were computed for 750,000 men and women. Data came from the American Cancer Society's prospective study, conducted in 1960-1972. Males who were 40% or more overweight had a mortality ratio of 1.87 for all causes of death. The ratio in women was 1.89. High mortality ratios were also observed in overweight men and women who died of coronary heart disease, diabetes and digestive diseases. The mortality ratio for cancer in obese men was 1.33; 1.55 for obese women. Sites with high mortality ratios in obese males were colon-rectum and prostate; in women, endometrium (about 5 times as high as for average weights); cervix (2 times as high), gall bladder (3.5 times), ovary (mortality ratio of 1.6) and breast cancer (mortality ratio of 1.5).

Body Weight↗

Histologic changes in pancreas in relation to smoking and coffee-drinking habits.

Histologic alterations in the epithelium of the ducts and exocrine portions of the parenchyma and thickening of the walls of the arterioles and arteries in the pancreas in relation to smoking habits was studied in 22,344 slides from 560 autopsied subjects. Only 5.4% of the nonsmokers had medium to high percentages of ductal cells with atypical nuclei. This rose to 50.7% in light smokers and to 74.9% in 40+ a day smokers. Advanced findings (increased numbers) of cells with atypical nuclei were found in the acinar cells of the parenchyma in only 1.8% of nonsmokers; 11.4% in less than 20 cigarettes a day smokers; 29.2% in 20-39 a day smokers; and 69.1% in 40+ a day smokers. Moderate or advanced hyaline thickening of arterioles in 12.8% of the nonsmokers increased to 74.4% in the heaviest smoking group. A similar relationship was observed for fibrous thickening in the arteries. Coffee drinking was not related to histologic alterations in the cells within the pancreas.

Adult↗

Artificial sweetener use and one-year weight change among women.

Weight change over a 1-year period was examined in a highly homogeneous group of 78,694 women ages 50-69 enrolled in a prospective mortality study. Artificial sweetener usage increased with relative weight and decreased with age. Users were significantly more likely than nonusers to gain weight, regardless of initial weight. Average weight gains or losses by artificial sweetener users differed by less than 2 pounds from gains or losses among nonusers. These results were not explicable by differences in food consumption patterns. The data do not support the hypothesis that long-term artificial sweetener use either helps weight loss or prevents weight gain.

Aged↗

Magnesium in cardiac energy metabolism.

Free intracellular magnesium ion, which influences many metabolic processes, is the subject of ongoing research. Its concentration has been difficult to measure because the available methods, including dye injection, microelectrodes, and nuclear magnetic resonance measurements, are invasive or indirect. Concentrations ranging from 0.1 mM in frog muscle to 6 mM in barnacle muscle have been reported. We describe recent experimental evidence regarding the concentration of free intracellular magnesium and consider the limitations of these methods. A substantial body of evidence, including our models of cardiac energy metabolism and its magnesium-related processes, indicates that intracellular concentrations of free magnesium are low (ca. 0.4 mM) and vary with time and conditions.

Animals↗

Contribution of passive smoking to respiratory cancer.

This article reviews data from experimental and epidemiologic studies on passive smoking and makes 12 recommendations for further study. The physicochemical nature of passive smoke, the smoke inhaled by nonsmokers, differs significantly from the mainstream smoke inhaled by the active smoker. At present, measurement of urinary cotinine appears to be the best method of assessing exposures to passive smoking. Data indicate that the greater number of lung cancers in nonsmoking women is probably related to environmental tobacco smoke. Exposures in utero and very early in life to passive smoking may be important in relationship to the subsequent development of cancer and need further consideration. The short-term effects of environmental tobacco smoke on the cardiovascular system, especially among high-risk individuals, may be of greater concern than that of cancer and requires further study. Further study of increased risks of lung cancers in relation to environmental tobacco smoke exposure requires larger collaborative studies to identify lung cancer cases among nonsmokers, better delineation of pathology, and more careful selection of controls. In addition, studies of epithelial cells or specific cytology should be undertaken to determine evidence of cellular changes in relation to environmental tobacco smoke exposure. Animal inhalation studies with passive smoke should be initiated with respect to transplacental carcinogenesis, the relationship of sidestream smoke exposure with lung cancer, the induction of tumors in the respiratory tract and other organs, and the differences in the physicochemical natures of sidestream and mainstream smoke.

Air Pollutants↗

Smoking habits and tar levels in a new American Cancer Society prospective study of 1.2 million men and women.

In 1982 the American Cancer Society (ACS) enrolled over 1.2 million American men and women in a prospective mortality study of cancer and other causes in relation to environmental and life-style factors. Biennial follow-up is planned through 1988. At the time of enrollment, 23.6% of the men and 20.0% of the women were current smokers of cigarettes. Compared with a similar ACS study of 1 million subjects enrolled 23 years earlier, among men the proportion of current smokers was halved and that of ex-smokers doubled, while among women the proportion of ever-smokers increased by 10% and that of ex-smokers quadrupled. Most smokers of filter cigarettes had smoked nonfiltered cigarettes earlier in life. The median year for switching to filters was 1964, the year of the first Surgeon General's report. More than one-third of male smokers' and one-half of female smokers' current brands had tar yields below 12 mg; less than 9% of male smokers' and 4% of female smokers' current brands had tar yields of 20.2 mg or more (nonfilters). The study population differed in many respects from the general U.S. population; the study population had, for example, a much higher average educational level. Nevertheless, distributions of smoking habits changed a few percentage points after adjustment to the educational level of the general population.

Adult↗

Overweight and cancer.

In a prospective study, mortality ratios were computed in relation to overweight, cancer, and other diseases. The study included 750 000 men and women followed for 12 years. Each person was given a weight index. Death rates for overweight and underweight persons were compared with rates for persons of average weight. Men who were 40% or more overweight had a mortality ratio for cancer of 1.33; women, 1.55. This ratio was much lower than that for coronary heart disease (men, 1.95; and women, 2.07); diabetes (5.19 and 7.90), and digestive diseases (3.99 and 2.29). Overweight men had significantly higher mortality ratios for colorectal and prostate cancer; overweight women had much higher rates for cancer of the endometrium, gall bladder, and cervix; and also significantly higher rates for ovary and breast cancer.

Adult↗

Magnesium regulation of the glycolytic pathway and the enzymes involved.

Past work, including our computer simulation of cardiac energy metabolism, indicates that magnesium is an important coherent controller of glycolysis and the Krebs cycle. Many of the glycolytic enzymes are sensitive to Mg2+. The most important effect is due to MgATP2-being a cofactor for a number of these enzymes while other chelation forms are inactive or inhibitory. The means by which Mg2+ and Mg2+ chelates of adenine nucleotides regulate the most important glycolytic enzymes--hexokinase, phosphofructokinase, aldolase, phosphoglycerate kinase, and pyruvate kinase--are described in detail. Creatine kinase, which is important in energy metabolism and highly sensitive to both metal ions and pH, is also discussed. It is necessary to properly control the composition of assay mixtures (particularly with regard to metal ions) in order to determine what actually regulates the activity of an enzyme.

Adenosine Diphosphate↗

Involuntary smoking and lung cancer: a case-control study.

In a case-control study in 4 hospitals from 1971 to 1981, 134 cases of lung cancer and 402 cases of colon-rectum cancer (the controls) were identified in nonsmoking women. All cases and controls were confirmed by histologic review of slides, and nonsmoking status and exposures were verified by interview. Odds ratios (OR) increased with increasing number of cigarettes smoked by the husband, particularly for cigarettes smoked at home. The OR for women whose husbands smoked 20 or more cigarettes at home was 2.11 (95% confidence limits: 1.13, 3.95). A logistic regression analysis showed a significant positive trend of increasing risk with increased exposure to the husband's smoking at home, controlled for age, hospital, socioeconomic class, and year of diagnosis. Comparison of women classified by number of hours exposed a day to smoke in the last 5 years and in the last 25 years showed no increase in risk of lung cancer.

Adult↗

Histologic type of lung cancer and asbestos exposure.

The histologic types of lung cancer in 855 patients (747 men and 107 women) from three hospitals and one international study of insulation workers were evaluated. Of these, 196 cases had asbestos exposure. About one half of the cases were diagnosed from surgical slides and one half from autopsy slides. Squamous cell carcinoma constituted the largest percentage of tumor types and was found with the same frequency in exposed and nonexposed groups. Small cell carcinoma was found in 25% of the exposed and in 15% of the nonexposed patients. Upper lung sites were involved in about two thirds of the cases with asbestos exposure and lower lobes in the other one third. There was little difference in histologic type in cases regardless of whether upper or lower lobes were involved. Cigarette smokers who smoked until their cancer diagnosis showed no difference in histologic type by amount smoked, and slight but not statistically significant differences from ex-cigarette smokers.

Adenocarcinoma↗

Calculation of free-Mg2+ concentration in adenosine 5'-triphosphate containing solutions in vitro and in vivo.

We have attempted to resolve the differences between the levels of free Mg2+ in muscle calculated by Wu et al. [Wu, S. T., Pieper, G. M., Salhany, J. M., & Eliot, R. S. (1981) Biochemistry 20, 7399-7403] (2.5 mM in guinea pig heart) and by Gupta and Moore [Gupta, R. K., & Moore, R. D. (1980) J. Biol. Chem. 255, 3987-3993] (0.6 mM in frog skeletal muscle) on the basis of substantially identical measurements by 31P NMR of the phosphate peaks in the spectrum of MgATP2-. The differences depend on the methods of calculation, including which reactions in which multiple equilibria are being considered. Biochemists and physical chemists customarily use different working definitions of the stability constant for MgATP2- in particular. Wu et al. used in their calculations, without reconciliation, methods involving three different operational definitions of the chelation equilibria involved. An algorithm for calculating Mg2+ and total ATP, which can be carried out with a hand calculator, is described here. With it, we calculated Mg2+ levels that agree with those determined by Gupta et al. [Gupta, R. K., Benkovic, J. L., & Rose, Z. B. (1978) J. Biol. Chem. 253, 6165-6171] with their in vitro systems. We therefore agree with the finding of Gupta and Moore that the Mg2+ level in skeletal and cardiac muscle is 0.6 mM.

Adenosine Triphosphate↗

Cancer mortality among woodworkers.

The mortality experience of 10,322 men employed in woodworking industries was compared with that of 406,798 nonwoodworkers. All subjects were enrolled in an American Cancer Society study and followed prospectively from 1959 through 1972. Age-adjusted rates of death from all causes and from all cancers were not higher in the woodworker group, but excess rates were observed for cancers of the lung, stomach, and bladder, as well as nonmelanoma skin cancer and possibly leukemia. Woodworkers experienced significantly decreased rates of colon-rectum cancer and coronary heart disease. The elevated cancer rates could not be explained by cigarette smoking habits. If anything, there is evidence to suggest a possible interaction between employment in woodworking trades and heavy cigarette smoking, in increasing the risk of lung and bladder cancer.

Adult↗

Cigarette smoking and coronary heart disease in blacks: comparison to whites in a prospective study.

The American Cancer Society's prospective study of 1 million Americans was analyzed to determine whether coronary heart disease (CHD) mortality rates by cigarette smoking in blacks differed from those in whites. More than 22,000 blacks were followed up for nearly 200,000 person-years in the 12-year study, 1960-1972. A total of 642 black males and 487 black females who died of CHD at age 40 years and older were included. CHD mortality ratios by number of cigarettes smoked were about the same at given smoking levels in black and white males and were slightly lower in black than in white females. The combined effects of a history of high blood pressure and other cardiovascular disease with smoking elevated the risk of dying of CHD, particularly in persons under age 65 years at the start of the study. In black females under 65 years of age who smoked cigarettes and had a history of these diseases, the CHD rate was 7.3 times higher than in white females who did not smoke and had no history of these diseases. The effect of other smoking variables and of exercise and overweight on the differences in rates between blacks and whites is also discussed.

Adult↗

Passive smoking and cancer--American experience.

Although one U.S. case-control study has shown that nonsmoking women married to smokers have a greater risk of lung cancer than do nonsmoking women married to nonsmokers, data from the American Cancer Society's prospective study have failed to show such risk: and, a case-control study based on reports of whether or not nonsmoking women and men were exposed to smoke of others also failed to show an elevated risk of lung cancer. Data presented here indicate that 40-50% of nonsmoking American women married to nonsmokers may be exposed to passive smoke. More studies are needed to demonstrate the role of passive smoke in the development of lung cancer in nonsmokers. The American Cancer Society is currently collecting such data in a case-control and a prospective study.

Colonic Neoplasms↗

Computer modeling identifies glucokinase as glucose sensor of pancreatic beta-cells.

Previous work from this laboratory indicates that glucokinase serves as the glucose sensor of pancreatic islets. Here we show by nonlinear computer optimization that the kinetic properties of glucokinase (together with hexokinase, known to be present in islets) account for the observed glycolytic rates in islets as a function of glucose level. Alternative enzymes that have been suggested to perform the same function as glucokinase, N-acetyl-D-glucosamine kinase and glucose-6-phosphatase, are shown to have incompatible properties, including a poor fit, different curve shapes, and unreasonable parameter values resulting from optimization. Their activities in islets are shown to be too low to account for observed glucose usage rates. This work endorses our previous proposal that glucokinase acts as the glucose sensor in pancreatic islet cells.

Blood Glucose↗