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Biomedical subjects

L M Brown

Publications and source records attributed to L M Brown.

At least 145 records · Page 8Linked to original sources

Lung cancer among long-term steel workers.

A case-control study in an industrialized area of eastern Pennsylvania involving interviews with the next of kin of 335 men who died of lung cancer and of 332 controls who died of other causes revealed a significantly increased risk associated with employment in the steel industry, the area's major employer. The excess was primarily among long-term employees, particularly those who began work before 1935. Adjusted for cigarette smoking, the odds ratio associated with career employment was 1.8 (p = 0.01, 95% confidence interval, 1.2, 2.8). The increase was higher among steel workers who worked in foundry operations, but was seen for broad categories of jobs within the industry. No significant associations were found for other industries, although a 60% increase (p = 0.27, 95% confidence interval, 0.7, 3.7) was noted for zinc smelter workers employed at least 15 years. The findings help clarify the role of occupation as a risk factor for lung cancer in the area, and suggest that exposures in the steel industry contribute to an extent greater than previously recognized.

Adult↗

Information available from surrogate respondents in case-control interview studies.

Epidemiologic studies of fatal diseases often require that information be sought from relatives or friends of deceased or disabled patients. The authors have evaluated the ability of several types of surrogate respondents to provide information on the smoking, occupational, medical history, and demographic characteristics of their next of kin in three recent case-control studies involving interviews with 2606 individuals. The ability of the surrogates to provide this information varied by topic, degree of detail requested, race, sex, age, and study area, but was most affected by the type of respondent. Sibs were best able to respond to questions about the subject's immediate family or events that occurred during early life, while spouses and offspring were best able to describe events that occurred during adult life. Several recommendations are made to improve the design of future interview studies.

Black or African American↗

Occupation and the high risk of lung cancer in Northeast Florida.

A case-control study involving interviews with 321 male patients with lung cancer and 434 controls, or their next of kin, was undertaken to identify reasons for the high lung cancer mortality along the northeast coast of Florida. In Duval county (Jacksonville), the age-adjusted rate for lung cancer, 1970-1975, among white males was the highest of all urban counties in the United States. Increased risks on the order of 40-50% were associated with employment in the shipbuilding, construction, and lumber/wood industries, particularly among workers with reported exposures to asbestos or wood dust. Excess risks were also linked to fishing and forestry occupations, although the numbers of cases involved were small. Occupational factors did not appear to fully account for the area-wide excess of lung cancer, but no evidence was found to implicate smoking habits, migration patterns, or diagnostic and reporting practices as factors responsible for the exceptional mortality rates.

Aged↗

The destruction of cytochrome P-450 by alclofenac: possible involvement of an epoxide metabolite.

The metabolism of alclofenac (4-allyloxy-3-chlorophenyl acetic acid) and its ability to induce destruction of cytochrome P-450 was studied in mouse hepatic microsomes obtained from control animals or animals pretreated with phenobarbitone (PB) or 3-methyl-cholanthrene (3-MC). No evidence was obtained for metabolism of alclofenac in control microsomes although in induced microsomes alclofenac was metabolised to both the dihydroxy (DHA) and phenolic (4-hydroxy-3-chlorophenyl acetic acid: HCPA) metabolites. Significant destruction of cytochrome P-450 was observed when alclofenac was incubated with microsomes from mice pretreated with PB but not from untreated or 3-MC-treated mice. This destruction is dependent on the presence of a NADPH-regenerating system and in inhibited in the presence of SKF-525A, metyrapone, glutathione and cysteine. The stable metabolites DHA and HCPA caused no loss of cytochrome P-450 whereas the reactive intermediate, alclofenac epoxide, was a potent inducer of destruction in the absence of NADPH. These results suggest that destruction of cytochrome P-450 by alclofenac in vitro is mediated, at least in part, through the formation of a reactive epoxide metabolite.

Animals↗

Branched skeletal muscle fibers not associated with dysfunction.

We report the occurrence of large clefts and branches in some amphibian vertebrate skeletal muscle fibers. Such fibers can be isolated intact from various skeletal muscles of fully mature animals and apparently are normal in other respects. Electron micrographs showed no signs of degeneration in most fibers. Electrical and mechanical studies revealed that all branches were excitable and able to contract. Branches evidently can arise in the absence of abnormal influences such as experimentally induced overload. The apparent cause may be either fusion or splitting of fibers.

Animals↗

Proliferation of pulmonary endothelial cells: time-lapse cinematography of growth to confluence and restitution of monolayer after wounding.

A fundamental characteristic of vascular endothelium is that it exists as a monolayer, a condition that must be met in both vascular growth and repair. Maintenance of the monolayer is important both for the exchange of nutrients and for interactions between blood solutes and endothelial enzymes and transport systems. We have used time-lapse cinematography to compare proliferative behavior of bovine pulmonary endothelial cells in (1) establishment of a monolayer from a low-density seed (7.5 X 10(4) cells in a 60 mm dish) and (2) restitution of a confluent monolayer (approx. 2.9 x 10(6) cells in a 60 mm dish) following a mechanical wound (removal of cells from an area 5 x 15 mm by scraping). Culture 2 was not refed after wounding. In culture 2, approx. 30% of the cells accounted for repopulation (confluence in 40 hr). In culture 1, all cells entered into division. Participating cells of culture 2 began division immediately (69 divisions/filmed area in 10 hr, vs. four divisions in culture 1). Interdivision times (IDT) were longer and relatively constant in culture 1 until near confluence; none were less than 10 h, whereas in 2, 24% of the IDT's were less than or equal to 10 hr. Remarkably, IDTs of culture 2 decreased steadily until confluence was re-established. Cell migration in culture 1 was multidirectional while direction of migration in culture 2 was always into the wound area. Mean migration rate (MIG) in culture 2 was related to the site of origin of the cells, those dividing farthest from the unwounded area had fastest MIGs. Neither culture formed more than a single layer of cells. Although the cell kinetics of cultures 1 and 2 differed, the same goal, confluence, was achieved in either case.

Animals↗

Mathematical analysis of endothelial sibling pair cell-cell interactions using time-lapse cinematography data.

The sibling pairs from two different endothelial cell cultures were analysed by time-lapse cinematography. It was shown that wounded and regular (low density seeded) cultures differed in the behaviour patterns of their siblings. The cultures differed most significantly in the minimum interdivision time (IDT) which was 27% lower for the wounded culture. In the wounded culture there was a greater correlation of IDT values between sibling pairs. IDT values recorded both for paired and for unpaired cells were shorter for the wounded than for the regular culture. The mean IDT for unpaired cells was longer than the mean IDT for paired cells in the regular culture. Thus paired cells in the regular culture, had shorter IDTs, but not as short as in the wounded culture. It was significant that in the wounded culture the first generation of siblings were very close (less than 150 microns apart) at division. Overall the behaviour differences between the two cultures resulted in a higher rate of increase in cell numbers, and thus faster repair, of the wounded monolayer.

Animals↗

Methods of evaluating fetal lung maturity.

Respiratory distress syndrome occurs in infants born with immature lungs. The immature fetal lung lacks an adequate supply of surfactant, a phospholipid-rich substance which is produced in the type II cells of the alveolar epithelium. In the fetus, surfactant is secreted into the potential air spaces of the lung and passes into the amniotic fluid as gestation proceeds. It is now clear that most methods currently in use for assessing fetal lung maturity depend on the detection of a sudden release of surfactant into the amniotic fluid as the lung reaches a critical stage of maturity. These methods, which include the lecithin/sphingomyelin ratio, the lung profile, total phospholipid or lecithin concentration, fluorescence depolarization, lamellar body phospholipid concentration, and the "shake" test, are reviewed in the light of recent understanding of the nature of surfactant. In assessing each method, we have examined possible sources of error in performing the test in the laboratory, factors which could theoretically limit its ability to reflect the state of fetal lung maturity and current information regarding its reliability, in terms of clinical performance. Guidelines for future research in this area are also suggested.

Amniotic Fluid↗

Improved procedure for lecithin/sphingomyelin ratio in amniotic fluid reduces false predictions of lung immaturity.

Many laboratories have found that their procedure for determining lecithin/sphingomyelin (L/S)ratios gives an unacceptably high proportion of false predictions of fetal lung immaturity. We investigated each step in the procedure, in an attempt to improve the clinical performance of the test and to make the method more amenable to standardization between laboratories. L/S ratios were determined by the new procedure in amniotic fluid from 147 pregnancies, collected within two days of delivery of the infant. Four cases had an L/S ratio less than 2; all developed hyaline membrane disease. No other cases of hyaline membrane disease were encountered in this study. For 106 of these pregnancies, the L/S ratio was also determined by the procedure previously in use. This predicted lung immaturity for 16 infants, only four of whom developed hyaline membrane disease. All 12 cases incorrectly predicted as immature by the old procedure were correctly classified by the new procedure.

Amniotic Fluid↗

Sedimentation of lung-derived phospholipid during low-speed centrifugation of amniotic fluid.

In most methods proposed for the assessment of fetal lung maturity, amniotic fluid is subjected to a preliminary low-speed centrifugation in an attempt to separate whole cells and cell debris from lung-derived surfactant phospholipid (lamellar body phospholipid). However, because lamellar body phospholipid is present in amniotic fluid in a membranous or particulate form, it is also partly sedimented by this procedure. The sedimentation of total phospholipid and lamellar body phospholipid by low-speed centrifugation has been quantitated for 49 samples of amniotic fluid from pregnancies of 30--41 weeks gestation. Isopycnic density-gradient centrifugation in a small air-driven ultracentrifuge was used to isolate lamellar body fractions from whole and centrifuged amniotic fluid. Centrifugation for 5 min at 1000 x g removed 0--70% of total phospholipid or lamellar body phospholipid, the mean values being 34 or 29%, respectively. There was an appreciable increase in lamellar body phospholipid relative to total phospholipid as a result of centrifugation in only 51% of the samples. In general, the effects of centrifugation were not related to gestational age of the fetus or the state of maturity of its lungs.

Amniotic Fluid↗

Membrane-bound glycoprotein in the alveolar cells of the caprine lung.

An ultramicroscopic analysis of caprine lung glycoproteins, designed to detect plasmalemma-associated sulfoglycoprotein of alveolar type I and alveolar type II cells, was performed. High-iron diamine staining demonstrated a layer containing sulfated glycoproteins at the atypical plasmamembrane of alveolar type I cells and microvilli of alveolar type II cells. The cytoplasmic vesicles of the alveolar type I cell contained the reaction product on the inner leaflet of the vesicular unit membrane. The vesicles showed a variety of interactions with the apical plasma membrane. High-iron diamine staining also demonstrated sulfoglycoproteins in the cytoplasmic granules of the mast cells in the alveolar septum. The present study gives evidence that plasmalemma of the alveolar cells of the goat lung possesses exposed hyaluronic acid groups.

Animals↗

The pathophysiology of arthrogryposis multiplex congenita neurologica.

Eleven patients with arthrogryposis multiplex congenita neurologica have been reviewed. Distinct patterns of deformity and muscle activity were identified which have been correlated with specific levels of segmental neurological motor deficit without sensory loss. The clinical picture was consistent with localised lesions of the anterior horn cell cell columns. This finding agreed with the recorded pathological lesions. Orthopaedic treatment should take account of the paralytic nature of the deformities.

Adolescent↗

Is the L/S ratio really a lecithin/sphingomyelin ratio?

Fetal lung maturity is commonly assessed by determining the ratio of lecithin/sphingomyelin in centrifuged amniotic fluid. In a variety of chromatographic systems currently used for the routine determination of the lecithin/sphingomyelin ratio, including the systems recommended in the original procedure, at least one and frequently two additional phospholipids, normally present in amniotic fluid, tend to chromatograph between or overlapping with lecithin and/or sphingomyelin. These phospholipids have been tentatively identified as phosphatidylserine and phosphatidylinositol. The extra phospholipids contribute significantly to the routine lecithin/sphingomyelin ratio with considerable variation between individual cases. Treatment of dried lipid extracts with cold acetone before chromatography, as suggested in the original lecithin/sphingomyelin ratio procedure, does not remove the interfering phospholipids.

Amniotic Fluid↗