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Biomedical subjects

L Garfinkel

Publications and source records attributed to L Garfinkel.

At least 73 records · Page 4Linked to original sources

Computer modeling of muscle phosphofructokinase kinetics.

The kinetics of the phosphofructokinase reaction were studied by computer modeling. A general random order, two-state allosteric model, of which the Monod--Wyman--Changeux model is a limiting case, was found to most accurately reproduce the experimental observations of Pettigrew & Frieden (1979 a,b). A simplified model with Hill coefficients was found to fit almost as well. In these models substrates bind preferentially to and stabilize the enzyme in the R state, and ATPH3-, the inhibitory species, binds preferentially to and stabilizes the enzyme in the T state. Enzymatic activity is regulated by conversion from the R to the T state, which is effected by protonation, especially of the uncomplexed enzyme, but the experimental data are inadequate for accurate estimation of the pKa of the enzyme. Random order binding of substrates is an important cause of sigmoidal kinetics. Additional experiments that would aid in the discrimination among rival models are described.

Adenosine Triphosphate↗

13-cis retinoic acid and murine pulmonary adenomas: a preliminary report.

The inhibitory effect of 13-cis-retinoic acid was tested in conjunction with ethyl carbamate (urethane) induced murine pulmonary adenomas. Continuous feeding of the retinoic acid for 20 weeks did not significantly reduce the number of surface adenomas. No physical evidence of toxicity due to the vitamin A analog was observed in any of the mice. All mice showed a steady weight gain during the 20-week period, and there was no evidence of eye lesions, hemorrhage, bone fractures, fur changes or lethargy.

Adenoma↗

Time trends in lung cancer mortality among nonsmokers and a note on passive smoking.

Lung cancer mortality rates were computed for nonsmokers in the American Cancer Society's prospective study for three 4-year periods from 1960 to 1972 and in the Dorn study of veterans for three 5-year periods from 1954 to 1969. There was no evidence of any trend in these rates by 5-year age groups or for the total groups. No time trend was observed in nonsmokers for cancers of other selected sites except for a decrease in cancer of the uterus. Compared to nonsmoking women married to nonsmoking husbands, nonsmokers married to smoking husbands showed very little, if any, increased risk of lung cancer.

Adult↗

Mortality and type of cigarette smoked.

Twenty-five years ago, cigarette smokers in the United Kingdom smoked plain cigarettes with an average tar yield of probably about 35 mg. Now smokers predominantly smoke filter cigarettes and average tar yields have been reduced by half. Epidemiological evidence comparing mortality in smokers of differing types of cigarettes is reviewed. Compared with smokers of higher tar plain cigarettes, smokers of lower tar filters cigarettes have a reduced mortality for lung cancer, for cancer of the buccal cavity, pharynx, larynx, oesophagus, and bladder, for chronic bronchitis and emphysema, and for cirrhosis of the liver. They also have a slightly significant. Problems of interpretation and limitations of the available evidence are discussed. No worthwhile evidence is yet available on smokers of "low tar' (0-10 mg) cigarettes and data are sparse on lifetime smokers of filter cigarettes. Continuing research is important to understand the situation fully, but the trends of lower mortality to be associated with lower tar and nicotine levels are promising.

Coronary Disease↗

Presence of asbestos bodies in organs other than the lung.

This study was designed to test the hypothesis that subjects with many asbestos bodies in their lungs at autopsy would also have asbestos bodies in various other organs. The subjects included 19 cases with diagnosis of asbestosis at death (two of these had mesothelioma, five had lung cancer) and 18 with pleural plaques but not asbestosis. Occupational histories were obtained from relatives. In subjects occupationally exposed to asbestos, large numbers of asbestos bodies were found in the lungs, and in most of these, asbestos bodies were found in many of the other organs examined. In the 18 cases with only pleural plaques found at autopsy, considerably fewer asbestos bodies were found in the lungs. The number of other organs with one or more asbestos bodies ranged from 32 percent to 62 percent of the sites examined. The findings seem to confirm the hypothesis of the study.

Aged↗

Atherosclerosis and aneurysm of aorta in relation to smoking habits and age.

A direct relationship between the extent of atherosclerotic lesions and smoking habits and age was found in a study of 1,412 aortas collected at autopsy from male patients from 1965 to 1970. The extent of the lesions was recorded using grading systems for formation of plaques, ulceration, and calcification. These findings increased with the number of cigarettes smoked and were greater in ex-cigarette smokers and pipe or cigar smokers than in nonsmokers. More extensive alterations were found in the abdominal aorta than in the thoracic aorta. Aneurysms were found eight times more frequently among those smoking one to two packs of cigarettes per day than in nonsmokers. Black subjects showed about one-half the number of aneurysms and fewer extensive atherosclerotic lesions than white subjects. At ages over 65 years, abdominal aortic aneurysms were found in 11 percent of all men and in 16 percent of the heavy smokers.

Age Factors↗

Mortality among California Seventh-Day Adventists for selected cancer sites.

In previous reports concerning cancer among Seventh-Day Adventists (SDA), comparisons were made only with the general population. This report compared California SDA to a sample of non-SDA who were demographically similar to SDA. The study consisted of 17 years of follow-up (1960--76) on 22,940 white California SDA and 13 years of follow-up (1960--72) on 112,725 white California non-SDA. Both groups completed the same base-line questionnaire in 1960. Deaths were ascertained by annual contacts with each study member and by computer-assisted record linkage with the California State death certificate file. Results indicated that, with the exception of colon-rectal cancer and smoking-related cancers, the difference in risk of fatal cancer between SDA and non-SDA was substantially reduced when SDA were compared with a more socioeconomically similar population. The persistence of the low risk for colon-rectal cancer can probably be attributed to some aspect of the diet or life-style of the SDA.

Adult↗

Cancer mortality in nonsmokers: prospective study by the American Cancer Society.

Standardized mortality ratios (SMR) were computed for nonsmokers who were compared with the total American Cancer Society study population for sites of cancer. The SMR were 64 for males and 96 for females for total cancer. Sites with low SMR in males (< 30) included lung, larynx, pleura, tongue, mouth, and pharynx. SMR less than 60 were observed for cancers of the esophagus and bladder. For female nonsmokers, relatively low SMR were observed for lung, larynx, and pharynx cancers. Death rates for cancers of all sites in females exceeded those in males in the age groups of 35--44, 45--54, and 55--64 years. Death rates were about the same in the 65- to 74-year-old group and about 40% higher in males than in females 75 years old and older. Lung cancer death rates in nonsmokers among both males and females were low and ranked between fourth and sixth in males and fifth to eleventh in females in the 5 age groups.

Adult↗

Computer simulation of the fructose bisphosphatase/phosphofructokinase couple in rat liver.

Recycling of fructose 6-phosphate and fructose 1,6-bisphosphate in the rat liver under gluconeogenic and glycolytic conditions was investigated with a computer model containing representations of the kinetic properties of phosphofructokinase and fructose 1,6-bisphosphatase under realistic physiological conditions. The two enzyme submodels were constructed from data for the isolated enzymes in vitro by formal optimization. Tissue metabolite concentrations were corrected for cytosolic/mitochondrial compartmentation and effects of chelation and protonation equilibria. This model, which mostly considers the behavior of livers from starved rats, predicts negligible recycling under physiologically realistic conditions. Metabolic regulation of fructose 6-phosphate, the magnesium ion concentration and the distribution of adenine nucleotides appear to prevent operation of a 'futile cycle' in vivo. Rate-limiting chemical species were identified by sensitivity analysis.

Animals↗

Changes in bronchial epithelium in relation to cigarette smoking, 1955-1960 vs. 1970-1977.

To test the hypothesis that the reduction in tar and nicotine content of cigarette smoke that began in the 1950s should be reflected by the histologic changes in the bronchial epithelium of cigarette smokers, 20, 424 sections taken at autopsy from the bronchial tubes of 445 men (non-lung-cancer deaths) were examined microscopically in random order. There were 211 men who died in 1955-1960, of whom 154 smoked regularly, and 234 men who died in 1970-1977, of whom 181 were regular smokers. Changes studied included basal-cell hyperplasia, loss of cilia and occurrence of cells with atypical nuclei. In both periods studied these histologic changes occurred far less frequently in nonsmokers than in cigarette smokers and increased in frequency with amount of smoking, adjusted for age. Sections with advanced histologic changes in those dying in 1955-1960 occurred in 0 per cent of nonsmokers, in 2.6 per cent of those smoking one to 19 cigarettes a day, in 13.2 per cent of those smoking 20 to 39 and in 22.5 per cent of those smoking 40+ cigarettes a day. In those who died in 1970-1977 the percentages were 0, 0.1, 0.8, and 2.2, respectively.

Adult↗

Short and long sleep and sleeping pills. Is increased mortality associated?

Prospective epidemiologic data of the American Cancer Society disclosed that reported usual sleep durations among groups who complained of insomnia and sleeping pill use "often" overlapped with those of groups who had no complaints. Reports of insomnia were not consistently associated with increased mortality when several factors were controlled; however, men who reported usually sleeping less than four hours were 2.80 times as likely to have died within six years as men who reported 7.0 to 7.9 hours of sleep. The ratio for women was 1.48. Men and women who reported sleeping ten hours or more had about 1.8 times the mortality of those who reported 7.0 to 7.9 hours of sleep. Those who reported using sleeping pills "often" had 1.5 times the mortality of those who "never" used sleeping pills. These results do not prove that mortality could be reduced by altering sleep durations or by reducing hypnotic prescribing. Rather, studies are needed to determine the causes of these mortality risk factors.

Adult↗

Scar cancer of the lung: increase over a 21 year period.

In a review of 1,186 cases of lung cancer found amoung 7,629 autopsied cases over a 21 year period a total of 82 peripheral cancers related to scars were found, constituting 1% of the autopsied cases and 7% of the lung tumors. 15% of all lung tumors were peripheral (vs. bronchogenic) and the percentage rose from less than 7 in the time period of 1955 to 1960 to a little more than 23 in the 1970 to 1976 time period. 45% of all peripheral lung cancers originated in a scar. Less than 2% of all lung cancers were found associated with scars in the 1955 through 1959 time period. This increased to nearly 16% in the 1970 through 1975 time period. 72% of the scar cancers were adenocarcinomas and 18% were of squamous cell type. The rest were large cell undifferentiated carcinomas and none was oat cell or small cell type. Over three-quarters of these scar cancers were found in the upper lobes and more than half were related to infarcts. Less than a quarter were related to tuberculosis scars. No relationship was found between smoking habits and scar cancer.

Adenocarcinoma↗

Adenomatous lesions of the large bowel: an autopsy survey.

A comprehensive autopsy survey of the large bowel showed that adenomas were very common lesions occurring in about one-half of the 518 cases studied. The great majority were small adenomatous polyps (tubular adenomas), 86.7% measuring less than 10 mm in diameter. Adenomas with a more complex tubulovillous pattern were larger with a mean diameter of 19.0 mm. There was no apparent incresae in mean size of adenomas with age. Nineteen clinically unsuspected cancers were discovered. Fourteen (8 in situ and 6 invasive) cancers had areas of residual benign adenoma. Five invasive cancers had no residual benign component. No in situ carcinomas or small (less than 10 mm) invasive cancers not containing residual adenoma were found. The results suggest that, although adenomas of the large bowel are very common, the vast majority are simple adenomatous polyps which do not undergo progressive growth and malignant change. Conversely, it appears that cancers may arise from benign adenomas which have the characteristics of large size and a more complex villous architecture.

Adenoma↗