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Biomedical subjects

A Norman

Publications and source records attributed to A Norman.

At least 163 records · Page 9Linked to original sources

Antitumor activity of sodium linoleate.

To identify the components in a microsomal fraction from the small intestinal mucosa of mice that were responsible for preventing the proliferation of Ehrlich ascites tumor (EAT) cells, we subjected the fraction to thin-layer and gas chromatography. Assays for cytotoxicity against EAT cells in vitro indicated that linoleic acid, which was present in the free fatty acid fraction at a surprisingly high concentration, was probably the major component responsible for the antitumor activity. In further assays, using the water-soluble salt sodium linoleate, we found that sodium linoleate was more effective in vitro in killing human chronic lymphocytic leukemia lymphocytes than normal lymphocytes and mouse leukemic thymocytes than normal thymocytes. We also found that a single intraperitoneal injection of 1 mg of sodium linoleate into Swiss-Webster mice one day after the mice were inoculated with EAT cells increased the median survival from 18 (in the controls) to 48 days (in the treated mice) and prevented tumor growth completely in over 40% of the treated mice. These results are consistent with the hypothesis that linoleic acid plays a significant role in keeping the small intestine from developing primary cancers. Results also suggest a potential role for sodium linoleate in cancer therapy.

Animals↗

Postirradiation protection of chromosomes by linoleate.

Physiological concentrations of linoleate reduce the frequency of micronuclei and chromosome aberrations in mouse bone marrow cells in vivo and of micronuclei in human lymphocytes in vitro when administered one hour after exposure of the cells to gamma rays.

Animals↗

Prevalence of maternal Ro (SS-A) and La (SS-B) autoantibodies in relation to congenital heart block.

The prevalence of autoantibodies to ribonucleoprotein antigens in cases of congenital heart block was established using immunofluorescence, counterimmunoelectrophoresis, double immunodiffusion and Western blots. All of 35 mothers of babies with congenital heart block, none of five mothers of babies with other types of heart block, 10 of 29 women with connective tissue disease but no babies with heart block, four of 445 normal pregnant women and two of 109 healthy nonpregnant women had either Ro (SS-A) or La (SS-B) antibodies. Of 15 babies with congenital heart block, 10 of 10 who were less than 3 months old possessed antibody. Antibody titres in affected but not in normal infants were lower compared with their mothers' titres, suggesting deposition of antibodies in the baby's tissues. The findings indicate that placental transfer of anti-Ro (SS-A) or anti-La (SS-B) is essential for development of congenital complete heart block.

Antibodies, Antinuclear↗

The importance of genetics for the optimization of radiation therapy. A hypothesis.

There is growing evidence that a fraction of cancer patients, perhaps as high as 15%, is radiation sensitive because of the action of specific genes. It seems likely that in the near future we shall be able to identify these patients by DNA probes. Therefore, we have calculated the impact on radiation therapy of removing these patients and treating the rest more aggressively. In particular, we assumed that the radiation oncologist will treat with an effective therapeutic dose corresponding to a 5% risk of serious normal tissue injury. Our results, in several instances, show a considerable increase in local control when the 5, 10, or 15% of the most radiosensitive patients are removed from the treated group. This is so, even if we assume that the tumor cells, as well as the normal cells, in radiosensitive patients are more radiosensitive than the tumor cells in patients of normal radiosensitivity.

Female↗

Rupture of the posterior tibial tendon: CT and surgical findings.

Computed tomography (CT) was performed in 42 patients with 49 clinically suspected tears of the posterior tibial tendon. Twenty-eight of the 49 suspected tears were subsequently surgically explored and repaired. Three patterns of tendon abnormalities were recognized on CT scans: type I-intact, hypertrophied, heterogeneous tendon; type II-attenuated tendon; and type III-absence of a portion of a tendon. Types I and II correlated with partial rupture seen during surgery, and type III correlated with complete rupture of the tendon. CT findings were accurate in 96% of the patients who underwent surgery. In four cases (14%), tendon rupture was seen on CT scans, but the extent of the injury was underestimated and the rupture was misclassified. Reactive periostitis of the distal tibia was seen in 71% of diseased tendons and may represent an important factor in the diagnosis of tendon rupture.

Adult↗

Rupture of posterior tibial tendon: CT and MR imaging with surgical correlation.

Computed tomography (CT) and magnetic resonance (MR) imaging were performed in 32 cases of clinically suspected chronic tears of the posterior tibial tendon. Surgery was performed in 22 patients (69%). Each case was classified radiographically and surgically as normal or a type 1, type 2, or type 3 rupture. The sensitivity and specificity of CT were 90% and 100%, respectively, while those of MR imaging were 95% and 100%. The accuracy in detecting ruptures was 91% for CT and 96% for MR imaging. The overall accuracy, which reflected the percentage of cases correctly diagnosed as well as those correctly classified, was 59% for CT and 73% for MR imaging. Although the differences between the CT and MR imaging parameters were not statistically significant (possibly due to the small population), the results suggest that MR imaging is the method of choice for detecting ruptures of the posterior tibial tendon. MR imaging provided greater definition of tendon outline, vertical splits, synovial fluid, edema, and degenerated tissue. CT was superior to MR imaging in showing associated bone abnormalities such as periostitis, subtalar osteoarthritis, and subtalar dislocation.

Adult↗

Bile constituents in ascitic fluid.

Bile acids and other bile constituents were determined in serum and ascites from eight patients with liver cirrhosis and in ascites secondary to malignancy in six patients. In cirrhotic ascites, total bile acid levels averaged 53% of the serum levels. A positive correlation was evident between ascites and serum levels for both cholic and chenodeoxycholic acid. For cholic acid, the ascites to serum ratio was higher in all patients compared with the corresponding ratio for chenodeoxycholic acid. The ascites to serum ratios for glycine, taurine and sulphate conjugates were similar, no tendency being shown by any of the conjugates to leak more easily into ascites. The high levels of bile acids in cirrhotic ascites suggests that the abdominal cavity harbours a fraction of the bile acid pool, which should be taken into account when studying bile acid turnover in liver cirrhosis. Bilirubin levels in cirrhotic ascites averaged 24% of the serum values. A positive correlation between ascites and serum levels for unconjugated bilirubin was recorded, whereas the occurrence of bilirubin conjugates in ascites was variable. Albumin levels in cirrhotic ascites were 25% of the serum levels. The ascites to serum ratios for other proteins such as IgG, IgA and IgM and also cholesterol and phospholipids were lower than that for albumin. In malignant ascites, a pattern different from that in liver cirrhosis was seen, low bile acid levels being found. No difference between bilirubin levels was observed, while albumin and cholesterol levels were higher in malignant ascites, with no overlap between the patient groups. These results indicate that the complex mechanisms of ascites formation result in variable levels of bile constituents in ascitic fluid, which are further dependent on the underlying disease.

Aged↗

Transport of serum bile acids in patients with liver cirrhosis and hyperbilirubinaemia.

From 12 patients with liver cirrhosis and hyperbilirubinaemia, the different conjugates of bilirubin and bile acids in the serum were separated and determined. The serum of the patients contained varying amounts of unconjugated bilirubin, which was not correlated to total serum bilirubin. No correlation between bilirubin conjugates and different conjugates of bile acids could be found, indicating different elimination processes for these substances. To examine whether a changed plasma transport of bile acids, which may contribute to the different excretion pattern of bilirubin and bile acids, occurs in liver cirrhosis, the bile acids in the different serum lipoprotein fractions were determined in seven of the patients. It was found that 40% of serum bile acids were bound to serum lipoproteins, despite decreased serum lipoprotein levels. The degree of lipoprotein binding of bile acids was not correlated to total serum bile acid concentrations. Cholic acid conjugates were present to a higher extent in the lipoprotein fractions than those of chenodeoxycholic acid or of deoxycholic acid. Determination was made of the distribution of individual conjugates between different lipoproteins and it was found that most of the glycine conjugates were present in high density lipoprotein, whereas the main part of sulphates and taurine conjugates were present in low density lipoprotein. These results indicate that a higher fraction of bile acids in liver cirrhosis is transported by lipoproteins in plasma, which may be of importance for the hepatic elimination of bile acids in cases with this disease.

Adult↗

Lipoprotein-bound bile acids in serum from healthy men, postprandially and during fasting.

Individual bile acids were determined by gas-liquid chromatography in, very low density, low density and high density lipoprotein fractions obtained by sequential ultracentrifugation of serum from normal adults, both postprandially and during fasting. The lipoproteins were found to contain 22-34% of fasting serum bile acids. The observed postprandial increase in bile acids did not exhibit any shift in the ratio between lipoprotein bound- and non-lipoprotein-bound bile acids. Bile acids were present in all isolated lipoprotein fractions, high density lipoproteins containing the highest amounts. In the lipoprotein fraction, a higher percentage of cholate than of chenodeoxycholate was found.

Bile Acids and Salts↗

Serum bilirubin subfractions in patients with alcohol abuse during detoxication.

Sera were obtained from 41 alcohol abusers consecutively admitted for detoxication. Blood samples were withdrawn on the second, fourth and seventh days of abstention. Initial bilirubin values were moderately elevated in 10 patients. Determination of the bilirubin subfractions by high performance liquid chromatography showed elevated values of unconjugated (alpha), monoconjugated (beta), diconjugated (gamma) and albumin-bound (delta) bilirubin, in 8, 15, 4 and 15 patients, respectively. During abstention, the total bilirubin value normalized rapidly, only three patients still had values above the upper reference limit after 7 days. In patients with initially elevated values of bilirubin subfractions, only a few had elevated beta and gamma levels on the seventh day, whereas delta levels decreased at a slower rate and remained virtually unchanged. On admission, 27 patients exhibited elevated levels of serum bile acids; these values decreased during abstention and after 7 days only six patients had slightly elevated values. Only five patients had initially elevated levels of alkaline phosphatase (ALP). These became normalized in all but two patients during abstention. The results suggest that mild cholestasis is common among alcohol-abusers without clinically evident liver disease and that these changes are reversible on abstention.

Adult↗

A longitudinal study of cholinesterase changes in pregnancy.

Serum cholinesterase activity was measured at intervals before, during, and after 44 pregnancies in 43 women. Three patterns of change were seen: (a) A decline in activity after conception, with no return towards pre-conception values before delivery (20 pregnancies). (b) A decline in activity accompanied by a partial or complete return to pre-conception values before delivery (19 pregnancies). (c) Either no discernible decline or increased activity during gestation (five pregnancies). We saw no association between these patterns and either the sex of the child, parity, smoking history, or alcohol intake. However, the continuous decrease in cholinesterase activity occurred in the youngest group of women, a decrease followed by an increase in the intermediate age group, and no decrease at all in the oldest group. Although not all the age-related differences quite reached statistical significance, these findings suggest that the patterns of change may be determined by some aspect of maternal physical maturity.

Adult↗

Radiation dose enhancement therapy with iodine in rabbit VX-2 brain tumors.

Loading tissue with iodine enhances the radiation dose absorbed from low energy X-rays. In order to test whether this is a useful procedure for treating brain tumors, we infused radiographic contrast media into rabbits carrying VX-2 brain tumors and delivered 15 Gy of 120 kVp X-rays in 3 fractions to the tumor. From CT scans we estimated that the dose enhancement was approximately 30%. The median survival times, after tumor detection on CT, of untreated rabbits, treated with radiation alone, and treated with radiation plus contrast media were 3, 25.5, 38.5 days, respectively. The repeated infusion of contrast media, 3.5 g of iodine per kg of body weight, did not affect kidney function as measured by serum creatinine levels. This method of enhancing radiation dose in brain tumors therefore appears promising.

Animals↗

The induction of micronuclei in human lymphocytes by low doses of radiation.

The appearance of micronuclei (MN) is delayed with respect to cell division in populations of irradiated human lymphocytes, so that the length of time in culture, as well as the number of divisions, is a factor in MN assays. Using two assays that control for cell kinetics, we measured the yield of cells with MN exposed to graded doses of 60Co gamma rays and 90KVP X-rays. The yields showed a non-linear increase with dose. They can be represented by two straight lines: the one in the range below 0.15 Gy has a slight slope, the other in the range above 0.15 Gy has a significantly greater slope. The radical scavengers cysteamine and glycerol, which reduced the MN yields sharply at 3 Gy, were less effective at 0.3 Gy, indicating that terminal deletions arising from the direct ionization of DNA are a major source of the MN induced by low radiation doses. It is likely that the non-linear dose response is due to the saturation of a DNA repair process.

Cell Cycle↗

Estrogen receptor levels and survival of breast cancer patients. A study on patients participating in randomized trials of adjuvant therapy.

A series of 1,022 patients taking part in clinical trials to compare postoperative radiation therapy with postoperative CMF chemotherapy, and postoperative tamoxifen with no adjuvant therapy, had their tumors analyzed for estrogen receptor content. Isoelectric focusing of the receptor in polyacrylamide gel was used for receptor assay and the results were related to tumor DNA content. The estrogen receptor content was significantly correlated to prolonged survival both for premenopausal and postmenopausal women. It was confirmed that postmenopausal women have increased median receptor values, and for this group values of more than approximately 0.3 fmol per microgram DNA were correlated to prolonged survival. For premenopausal women, a lower level of more than 0.1 fmol per microgram of DNA defined patients with prolonged survival. Lymph node involvement and receptor level were independent prognostic indicators. Patients randomized to tamoxifen or CMF tended to live longer as compared with control patients but this was not statistically significant. Moreover, there was no tendency for adjuvant tamoxifen to further increase the survival of patients with receptor-containing tumors as compared with control patients with similar receptor values.

Adult↗