The incidence of X chromatin bodies and mitotic modifications and aberrations has been analyzed using Feulgen-squash preparations in 47 cervical cancers from Helsinki and 35 from Madison. Sixteen of the 82 tumors did not display any X chromatin bodies, and some others showed a lower than normal frequency, especially in the large nuclei. Different hypotheses to explain the absence of Barr bodies in female tumors have been reviewed. A new observation is that 44/82 tumors contained endomitoses. The metaphase/prophase ratio (M/P) was higher than 1.5 in all but three cases, reaching values as high as 23.0 (Madison) and 34.2 (Helsinki), and in one exceptional case, 51.8. The different types of cells, mitotic, endomitotic, and those with large to giant nuclei, form their own strands or layers. Cervical cancer is diagnosed earlier in Finland than in Madison due to a Pap mass screening program, and consequently, the survival of the patients after 5 years was 27/47 in Helsinki and 6/35 in Madison. No correlation could be established between the M/P (or other mitotic phenomena) or the stage and grade of the tumor, the age of the patient, or survival time.

Mitotic modifications and aberrations characteristic of human malignant tumors have been analyzed and illustrated in cervical cancer. Most of them can be explained by assuming that the coordination of the centrosomal and chromosomal mechanisms, typical of normal mitosis, is disturbed. When the spindle mechanism is ahead of the chromosomes, the prophase is relatively shortened. This expresses itself in an increase of the ratio of metaphases to prophases (M/P), which in normal tissues is around 1. With M/P values of 4-6, the first tripolar metaphases are formed, and with higher ratios, divisions having more and more poles appear. The spindle and the chromosomes are out of step in the opposite direction in endocycles, in which the spindle is slowed down or absent. The most common of the endocycles is endoreduplication, followed by endomitosis, which is found in more than half of the cervical cancers. Mitotic abnormalities include lagging chromosomes in metaphase and anaphase and bridges in anaphase, which, when numerous, may lead to restitution. More sporadically occurring are C-mitosis and other abnormalities, including cell and nuclear fusions. There is a wide range of variation in the occurrence and frequency of chromocenters within a tumor, and an even greater variation between tumors. About one-fifth of cervical cancers lack X chromatin bodies. The abnormal chromosome constitutions in cancer are the result of various mitotic modifications and aberrations, as well as chromosome rearrangements. New chromosome combinations are constantly created and selection promotes the fastest dividing ones, which, in turn, become new stem lines of the tumor.

Abstract. The urine and plasma content of certain proteins was studied near term in healthy gravidas, in gravidas with essential hypertension, proteinuria, hypertension of pregnancy and gestosis (pre‐eclampsia; toxaemia), besides this the ratio of urine‐plasma concentrations for each protein was calculated. In gestosis only the urine‐plasma ratio of ceruloplasmin differed from those of the other proteins, but in the other diseases studied this ratio showed no difference from that in healthy gravidas. The amounts of different proteins excreted in urine did not correlate with the molecular size of the respective protein.

Abstract. Systolic and diastolic blood pressure, urinary protein and amount of edema were compared with factors reflecting the prognosis and condition of the newborn in a series of 4404 patients with EPH‐gestosis, collected from the Helsinki University Central Hospital in 1965–1969 and the University Women's Clinic, Würzburg, in 1960–1969. No significant association was observed between slight and moderate edema and the prognosis of the newborn. The systolic blood pressure gave more significant information than the diastolic blood pressure. The amount of urinary protein showed the most consistent correlation with an impaired prognosis. The systolic blood pressure and proteinuria were thus the most significant indicators. An index for estimation of the prognosis in EPH‐gestosis was constructed on this basis. The purpose of this index is to provide a means of assessing the severity of the condition in the initial stage of treatment by exact use of simple observations. The index defines the risk of perinatal mortality, prematurity, asphyxia and smallness for dates in the individual case.

The effect of hormonal contraceptives on the vaginal smear pattern was studied by comparing cytological findings in 1012 patients using the combined type and 228 using the sequential type of oral contraceptives to cytological findings on record in 2480 controls. Comparisons by Papanicolaous classes showed no significant differences in frequency of suspicious or positive smears. Distribution of the series when vaginal flora were classified into grades as suggested by af Heurlin showed significant differences with controls predominating in grades 1 and 2 (normal vaginal microbiology) and combination oral patients predominating in grade 3. A lower incidence of Trichomonas was found in combination oral patients than in controls. Yeast infection and cytolysis were less common in sequential patients than in controls. Spermatozoa were found most frequently in patients taking sequentials.

Acta Obstetricia et Gynecologica ScandinavicaVolume 39, Issue 1 p. 153-168 Hormonal and Neurovegetative Factors in Myomagenesis Sakari Timonen, Sakari Timonen Women's Clinic, University of Helsinki, FinlandSearch for more papers by this authorEsko Purola, Esko Purola Women's Clinic, University of Helsinki, FinlandSearch for more papers by this author Sakari Timonen, Sakari Timonen Women's Clinic, University of Helsinki, FinlandSearch for more papers by this authorEsko Purola, Esko Purola Women's Clinic, University of Helsinki, FinlandSearch for more papers by this author First published: January 1960 https://doi.org/10.3109/00016346009157845Citations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume39, Issue1January 1960Pages 153-168 RelatedInformation

HereditasVolume 40, Issue 3-4 p. 313-324 Open Access THE PROPHASE INDEX AND THE OCCURRENCE OF MULTIPOLAR DIVISIONS IN HUMAN CANCER CELLS EEVA THERMAN, EEVA THERMAN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this authorSAKARI TIMONEN, SAKARI TIMONEN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this author EEVA THERMAN, EEVA THERMAN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this authorSAKARI TIMONEN, SAKARI TIMONEN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this author First published: September 1954 https://doi.org/10.1111/j.1601-5223.1954.tb02975.xCitations: 3AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Literature Cited 1 Bayreuther, K. 1952. Der Chromosomenbestand des Ehrlich-Ascites-Tumors der Maus. Ztschr. f. Naturforsch. 7 b: 554– 557. 2 Darlington, C. D. 1948. The plasmagene theory of the origin of cancer. Brit. Journ. Cancer 2: 118– 126. 3 Fardon, J. C. and Prince, J. E. 1952. A comparison of the ratios of metaphase to prophase in normal and neoplastic tissues. Cancer Research 12: 793– 795. 4 Koller, P. C. 1943. Origin of malignant tumour cells. Nature 151: 244– 246. 5 Koller, P. C. 1947a. Abnormal mitosis in tumours. Brit. Journ. Cancer 1: 38– 46. 6 Koller, P. C. 1947b. The experimental modification of nucleic acid systems in the cell. Symp. Soc. Exp. Biol. 1: 270– 290. 7 Levan, A. 1954. Colchicine-induced c-mitosis in two mouse ascites tumours. Hereditas XL: 1– 64. 8 Levan, A. and Hauschka, T. S. 1952. Chromosome numbers of three mouse ascites tumours. Hereditas XXXVIII: 251– 255. 9 Levan, A. and Hauschka, T. S. 1953a. Nuclear fragmentation — a normal feature of the mitotic cycle of lymphosarcoma cells. Hereditas XXXIX (Festskrift för Arne Müntzing 2.3.1953): 137– 148. 10 Levan, A. and Hauschka, T. S. 1953b. Endomitotic reduplication mechanisms in ascites tumours of the mouse. Journ. Nat. Cancer Inst. 14: 1– 43. 11 Lewis, M. R. and Lewis, W. H. 1932. Malignant cells of Walker rat sarcoma No. 338. Amer. Journ. Cancer 16: 1153– 1183. 12 Lewis, W. H. 1940. Some contributions of tissue culture to development and growth. Growth Suppl.: 1– 14. 13 Lewis, W. H. 1951. Cell division with special reference to cells in tissue cultures. Ann. New York Acad. Sciences 51: 1287– 1294. 14 Makino, S. A. 1952a. A cytological study of the Yoshida sarcoma, an ascites tumor of white rats. Chromosoma 4: 649– 674. 15 Makino, S. A. 1952b. Cytological studies on cancer. III. The characteristics and individuality of chromosomes in tumor cells of the Yoshida sarcoma which contribute to the growth of the tumor. Gann 43: 17– 34. 16 Makino, S. A. and Kanö, K. 1951. Cytological studies on cancer. II. Daily observations on the mitotic frequency and the variation of the chromosome number in tumor cells of the Yoshida sarcoma through a transplant generation. Journ. Fac. Science Hokkaido Univ. VI, 10: 225– 242. 17 Makino, S. A. and Yosida, T. H. 1951. Cytological studies on cancer. I. Morphological and statistical observations on the abnormal mitosis in tumor cells of the Yoshida sarcoma through a transplant generation. Journ. Fac. Science Hokkaido Univ. VI, 10: 209– 224. 18 Möllendorff, W. v. 1941. Zur Kenntnis der Mitose. X. Über Vorkommen pathologischer Mitosen in Gewebskulturen des Brown-Pearce Tumors. Zugleich ein Beitrag zur Frage der Tumormitosen. Ztschr. f. Zellforsch. u. mikr. Anat. 31: 60– 90. 19 Oksala, T. 1944. Zytologische Studien an Odonaten. II. Die Entstehung der meiotischen Präkozität. Ann. Acad. Scient. Fenn A IV, 5: 1– 33. 20 Oksala, T. 1953. Timing relationships in mitosis and meiosis. — Proc. IX Internat. Congress Genetics (in the press). 21 Peters, J. J. 1946. A cytological study of mitosis in the cornea of Triturus viridescens during recovery after colchicine treatment. Journ. Exp. Zool. 103: 33– 60. 22 Therman, E. and Timonen, S. 1950. Multipolar spindles in human cancer cells. Hereditas XXXVI: 393– 405. 23 Timonen, S. 1950. Mitosis in normal endometrium and genital cancer. Acta Obstetr. Gyn. Scand. 31, Suppl. 2: 1– 88. 24 Timonen, S. 1954. Comparison of the cytological and histological picture in cancer (in the press). 25 Timonen, S. and Therman, E. 1950. The changes in the mitotic mechanism of human cancer cells. Cancer Research 10: 431– 439. Citing Literature Volume40, Issue3-4September 1954Pages 313-324 ReferencesRelatedInformation

HereditasVolume 37, Issue 1-2 p. 266-279 Open Access INCONSTANCY OF THE HUMAN SOMATIC CHROMOSOME COMPLEMENT EEVA THERMAN, EEVA THERMAN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this authorSAKARI TIMONEN, SAKARI TIMONEN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this author EEVA THERMAN, EEVA THERMAN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this authorSAKARI TIMONEN, SAKARI TIMONEN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this author First published: February 1951 https://doi.org/10.1111/j.1601-5223.1951.tb02893.xCitations: 10AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Literature Cited 1 Andres, A. H. and Jiv, B. V. 1936. Somatic chromosome complex of the human embryo. Cytologia 7: 371– 388. 2 Clark, Frances J. 1940. Cytogenetic studies of divergent meiotic spindle formation in Zea mays. Amer. Journ. Bot. 27: 547– 559. 3 Darlington, C. D. 1937. Recent advances in cytology. 2nd ed. — London. 4 Darlington, C. D. and La Cour, L. F. 1947. The handling of chromosomes. — London. 5 Geitler, L. 1938. Chromosomenbau. — Berlin. 6 Huskins, C. L. 1947. The subdivision of the chromosomes and their multiplication in non-dividing tissues: possible interpretations in terms of gene structure and gene action. Amer. Nat. 81: 401– 434. 7 Huskins, C. L. 1948. Chromosome multiplication and reduction in somatic tissues. Nature 161: 80– 83. 8 Huskins, C. L. 1949. The nucleus in development and differentiation and the experimental induction of »meiosis». — Proc. 8th Int. Cong. of Gen. (Hereditas, Suppl. Vol.): 274– 285. 9 Jacobj, W. 1935. Die Zellkerngrösse beim Menschen. Ein Beitrag zur quantitativen Cytologie. Zschr. f. mikr.-anat. Forsch. 38: 161– 240. 10 Karplus, H. 1930. Ein Beitrag zur Kenntnis der somatischen Mitose beim Menschen. Zschr. f. Zellforsch. 10: 38– 52. 11 Kemp, T. 1930. Über die somatischen Mitosen bei Menschen und warm-blütigen Tieren unter normalen und pathologischen Verhältnissen. Zschr. f. Zellforsch. 11: 429– 414. 12 Koller, P. C. 1947. Abnormal mitosis in tumours. British Journ. Cancer 1: 38– 46. 13 Matthey, R. 1949. Les chromosomes des vertébrés. — Lausanne. 14 Oksala, T. 1939. Über Tetraploidie der Binde- und Fettgewebe bei den Odonaten. Hereditas XXV: 132– 144. 15 Oksala, T. 1944. Zytologische Studien an Odonaten. II. Die Entstehung der meiotischen Präkozität. Ann. Acad. Sci. Fennicae A IV 5: 1– 33. 16 Therman, Eeva and Timonen, S. 1950. Multipolar spindles in human cancer cells. Hereditas XXXVI: 393– 405. 17 Timonen, S. 1950. Mitosis in normal endometrium and genital cancer. Acta Obstetr. Gynecol. Scand. 31, Suppl. 2: 1– 88. 18 Timonen, S. and Therman, Eeva. 1950. The changes in the mitotic mechanism of human cancer cells. Cancer Research 10: 431– 139. 19 Wigglesworth, V. B. 1948. The role of the cell in determination. Symp. Soc. Exp. Biol. 2: 1– 16. 20 Winge, Ö. 1930. Zytologische Untersuchungen über die Natur maligner Tumoren. II. Teerkarzinome bei Mäusen. Zschr. f. Zellforsch. 10: 683– 735. Citing Literature Volume37, Issue1-2February 1951Pages 266-279 ReferencesRelatedInformation

Summary 1.The chromosomes in 35 cases of normal endometrium in the proliferation stage have been studied. In addition to the normal chromosome number, 48, both polyploid and hypoploid cells have been found. 2.The chromosome conditions in 174 cases of carcinoma of the female genital tract have been examined. Here also, cells from low hypoploids to very high polyploids have been observed. Other phenomena characterizing cancer cells are the occurrence of lagging chromosomes in the divisions, multipolar spindles, stickiness of the chromosomes, and the “colchicine-effect.” 3.The most constant features noticed in cancer cells are, however, the increased division rate of the cells and the changed relative duration of the different mitotic phases, as determined from their relative frequencies. In normal cells the prophase is usually a somewhat longer stage than the metaphase. In cancer tissue, it is much shortened—the metaphase, in this case, being of considerably longer duration. 4.On the above facts we present the following theory: The primary cytological change in cancer cells consists in an accelerated rate of the spindle mechanism. The intrachromosomal changes do not stand the pace, and thus the extrachromosomal changes become precocious in relation to them. From this original change, most of the other chromosomal aberrations can be derived. 5.Of the various theories concerning the origin of cancer our observations agree best with Darlington9s plasmagene theory.

HereditasVolume 36, Issue 4 p. 393-405 Open Access MULTIPOLAR SPINDLES IN HUMAN CANCER CELLS EEVA THERMAN, EEVA THERMAN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this authorSAKARI TIMONEN, SAKARI TIMONEN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this author EEVA THERMAN, EEVA THERMAN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this authorSAKARI TIMONEN, SAKARI TIMONEN WOMEN'S CLINIC, UNIVERSITY OF HELSINKI, FINLANDSearch for more papers by this author First published: October 1950 https://doi.org/10.1111/j.1601-5223.1950.tb03385.xCitations: 2AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL LITERATURE CITED 1 Bleier, H. 1930. Untersuchungen über das Verhalten der verschiedenen Kernkomponenten bei der Reduktionsteilung von Bastarden. La Cellule 40: 83– 144. 2 Bowen, R. H. 1922. Notes on the occurrence of abnormal mitoses in spermatogenesis. Biol. Bull. 43: 184– 202. 3 Darlington, C. D. 1937. Recent advances in cytology. 2nd ed. — London. 4 Darlington, C. D. 1948. The plasmagene theory of the origin of cancer. Brit. Journ. Cancer 2: 118– 126. 5 Darlington, C. D. and La Cour, L. F. 1947. The handling of chromosomes. — London. 6 Darlington, C. D. and Thomas, P. T. 1937. The breakdown of cell division in a Festuca-Lolium derivative. Ann. Bot. N. S. 1: 747– 761. 7 Fankhauser, G. 1934. Cytological studies on egg fragments of the salamander Triton. IV. The cleavage of egg fragments without the egg nucleus. Journ. Exp. Zool. 67: 349– 394. 8 Koller, P. C. 1943. Origin of malignant tumour cells. Nature 151: 244– 246. 9 Koller, P. C. 1947. Abnormal mitosis in tumours. Brit. Journ. Cancer 1: 38– 46. 10 La Cour, L. F. 1944. Mitosis and cell differentiation in the blood. Proc. Royal Soc. Edinburgh B 62: 73– 85. 11 Levine, M. 1931. Studies in the cytology of cancer. Amer. Journ. Cancer 15: 144– 211, 788–834, 1410–1494. 12 Lewis, M. R. and Lewis, W. H. 1932. The malignant cells of Walker rat sarcoma No. 338. Amer. Journ. Cancer 14: 1153– 1183. 13 Mather, K. 1948. Nucleus and cytoplasm in differentiation. Symp. Soc. Exp. Biol. 2: 196– 216. 14 Moellendorff, W. v. 1941. Zur Kenntnis der Mitose. X. Über das Vorkommen pathologischer Mitosen in Gewebskulturen des Brown-Pearce-Tumors. Zugleich ein Beitrag zur Frage der Tumormitosen. Zschr. f. Zellforsch. 31: 60– 90. 15 Oksala, T. 1944. Zytologische Studien an Odonaten. II. Die Entstehung der meiotischen Präkozität. Ann. Acad. Sci. Fennicae A IV 5: 1– 33. 16 Romeis, B. 1932. Taschenbuch der mikroskopischen Technik. 13th ed. — Munich and Berlin. 17 Schrader, F. 1946. Mitosis. — New York. 18 Swanson, C. P. and Nelson, R. 1942. Spindle abnormalities in Mentha. Bot. Gaz. 104: 273– 280. 19 Timonen, S. and Therman, E. 1950. The changes in the mitotic mechanism of human cancer cells. Cancer Research 10: 431– 439. 20 Wilson, E. B. 1925. The cell in development and heredity. — New York. 21 Winge, Ö. 1930. Untersuchungen über die Natur maligner Tumoren. II. Teerkarzinome bei Mäusen. Zschr. f. Zellforsch. 10: 683– 735. Citing Literature Volume36, Issue4October 1950Pages 393-405 ReferencesRelatedInformation