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Biomedical subjects

N Dahlmann

Publications and source records attributed to N Dahlmann.

28 records · Page 2Linked to original sources

Human serum deoxythymidine-5'-triphosphatase activity as a parameter in the diagnosis and follow-up of large bowel carcinoma.

Serum deoxythymidine-5'-triphosphatase (dTTPase) levels were determined in 71 patients with large bowel cancers at different clinical stages: 10 patients in Duke's Stage A; 37, in Duke's Stage B; and 24, in Duke's Stage C. The dTTPase values of patients in Duke's Stage B and C are significantly elevated over normal healthy controls, and a correlation was observed between tumor stage and dTTPase activity. While dTTPase levels rise in patients with increasing tumor burdens, they decline in patients with undetectable tumor tissue after radical surgery. Six of 15 courses are documented, illustrating that, after successful operation, enzyme levels revert to normal. In all patients, carcinoembryonic antigen levels were determined along with dTTPase values, and both sets of data were correlated with each other indicating a correlation coefficient of zero. So, if both dTTPase and carcinoembryonic antigen are taken into account, the sensitivity of detection of colorectal carcinomas rises to 66% for all patients and to 92% for patients with a colorectal carcinoma of Duke's Stage C.

Carcinoembryonic Antigen↗

Human serum thymidine triphosphate nucleotidohydrolase: purification and properties of a new enzyme.

Thymidine triphosphate monophosphohydrolase (dTTPase), an enzyme which catalyzes the hydrolysis of dTTP to the corresponding diphosphate (dTDP), has been purified to homogeneity from human serum. The enzyme sediments with 3.8 S in sucrose density gradients. A Stokes radius of 31 A is estimated by gel filtration. Accordingly, its molecular weight is 48 500. Since only one single band of Mr 24 000 is detected after sodium dodecyl sulfate/polyacrylamide gel electrophoresis, the native enzyme seems to be composed of two identical subunits. The enzyme exhibits optimal activity over a pH range from 7 to 9, and the activation energy is estimated to be 7.1 kcal/mol (29.7 kJ/mol) at pH 7.8. While the enzyme is active in the absence of added divalent cations, the activity can be inhibited by ethylenediaminetetracetic acid (EDTA) but not by phenanthroline. The inhibition caused by EDTA is reversed by Mn2+. Zn2+ causes a complete inhibition of enzyme activity. No requirement exists for a sulfhydryl compound. The enzyme has an Rf value of 0.45, an isoelectric point of 5.2, and an apparent Km value of 40 microM for dTTP. dUTP and UTP are degraded by about 50 and 20% of the rate of dTTP hydrolysis, respectively. Other deoxyribonucleosides or ribonucleoside triphosphates do not serve as substrates for the dTTPase. The existence of this enzyme is significant since it could play a role in the regulation of the cellular dTTP levels.

Humans↗

Influences of environmental conditions during infancy on final body stature.

In the following article we shall investigate the Second World War with its consequences on nutrition and other living conditions for the German population to try to determine whether lack of nutrition plus other deficiencies, which infants were subjected to in Germany during this time, had any influence on their adult stature. The following data formed the basis of our investigation: (1) nutrition of infants and school-aged children during the years 1939-1948; (2) stature and weight of 6-year-old boys between 1907 and 1948; (3) infant mortality between 1935 and 1950; (4) stature of 19-year-old men who were born between 1938 and 1951. From Figure 5 it can be seen that the mean stature of 19-year-old men born between 1938 and 1951 (except for those born in 1944 and 1945) rose steadily (secular acceleration). The plot of the yearly rate of acceleration (Fig. 6) reveals a minimum in 1944-1945, and follows a general downward, U-shaped trend (P less than 0.05). On the other hand, infant mortality between 1941 and 1949 follows an upward U-shaped trend (P less than 0.05). For the 6- to 8-month-old infants during 1945-1948 nutrition was far worse than that during the preceding years. It is even likely that the nutrition for the infants had already begun to decrease in quality in 1942. We find, therefore, a close correlation between the years of high infant mortality and the growth deficiencies of the men born during these years. Since we must assume that the nutritional situation for babies and infants worsened steadily after 1942 until it is apparent that a number of environmental factors directly influence human growth. The conclusion of our analysis is that a deficit of growth occurring after the end of the fourth year can be compensated fully. We conclude, furthermore, that the growth deficits which arise before the fourth year, on the other hand, cannot be compensated fully even if good or excellent environmental conditions follow.

Adolescent↗

[Infant development and adipositas (author's transl)].

The present paper tries to answer the question, how far the degree of adipositas during adult age can be affected by influences from early childhood. Our special interest concerned the relation between the number of fat cells and adipositas. To answer this question we had to clarify some methodical problems. The difficulty was to find out in a statistical way the part of fat tissue in total body weight. Therefore we introduced the idea of variability of tissues supposing that the different tissues can be influenced in a different way by environmental factors. Bone tissue turned out to be the most steady in contrary to fat tissue as the most unstable one. We stated the hypothesis that the differences between two groupes of equal sized individuals are based upon differences of fat tissue. Our material have been the age classes born in 1938 till 1951. Their environmental conditions during infancy and the age of 19 have been investigated. The result was that the conditions of life of 19-year-old men can be regarded as similar, whereas those of infants showed significant differences. The age classes 1945-1948 proved to be nourished more badly than the years before (1938-1944) and after (1949-1951). With these results corresponds stature, whereas no similar effects could be revealed in body weight. The conclusion of our paper is that regarding to adipositas no connection between infancy and adult age could be proved.

Adipose Tissue↗

Tumor markers in the diagnosis and follow-up of head and neck cancer: role of CEA, CA 19-9, SCC, TK, and dTTPase.

The clinical relevance of the carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, squamous cell carcinoma antigen (SCC), thymidine kinase (TK), and deoxythymidine-5'-triphosphatase (dTTPase) as tumor markers in the diagnosis and follow-up treatment of 26 patients with head and neck cancer is evaluated. Serum levels prior to treatment were found elevated just above the upper limit of normal in 46% (SCC), 15% (CEA), 12% (CA 19-9), 27% (TK), and 39% (dTTPase) of all patients. If all markers were taken into account, they were elevated in 73% of the untreated patients. However, only in a few cases were the tumor marker values elevated significantly (8%-12%). No significant correlation was detected between serum levels and tumor localization, staging, grading, or performance status for any of the markers. In the follow-up none of the markers tested revealed any disease-related information despite therapy variation. Patients with originally elevated marker levels showed decreasing and in some cases increasing values after primary therapy, although no tumor recurrence was detected. Even considering the results as preliminary due to the rather small sample size, they suggest that the routine assessment of CEA, CA 19-9, SCC, TK, and dTTPase serum levels is of limited practical value.

Antigens, Neoplasm↗

Serum deoxythymidine-5'-triphosphatase activity in lymphoproliferative disorders of men and mice.

A recently discovered enzyme of the pyrimidine pathway, deoxythymidine-5'-triphosphatase (dTTPase), was estimated in sera from leukemic mice and 64 untreated patients with non-Hodgkin's lymphoma (NHL) as well as 30 patients with plasmocytoma. At the age of 19 weeks the Mov-9 substrain of 129 mice developed leukemia in contrast to the congenic controls. Patient lymph node biopsies were classified according to the Kiel classification. The results showed a significant correlation between dTTPase activity and the onset of proliferation (studied in mice), as well as the grade of malignancy (studied in men). The more advanced the disease or the less aggressive the tumor, the higher the dTTPase activity. This gives rise to the speculation that dTTPase might be part of a control in the proliferation process.

Animals↗

Separation of deoxythymidine-5'-triphosphatase from unspecific hydrolases. A recommended micromethod in the diagnostic evaluation of human carcinoma.

A one-step micromethod was developed to separate from human serum four different enzymes capable of hydrolysing dTTP to the respective diphosphate. According to the purification procedure, the enzymes are referred to as Fraction I, II, IIIa, and IIIb, respectively. In view of a putative tumor specificity the activities of the enzymes are investigated for five different groups, epithelial carcinoma, leukemia, and three control groups. The results indicate that an absolute tumor specificity could not be attributed to one of the enzyme fractions. The activity of Fraction I is, however, highly elevated in the sera of seriously ill patients, whereas the activity of the epithelial carcinoma and the leukemia is even slightly reduced compared to the blood donor group. These data provide evidence that the determination of Fraction IIIb along with Fraction I can reduce the false positive rate to a great extent.

Humans↗