Selected subjects have been treated with cyclophosphamide and nitrogen mustard. The granulocytopenia has been followed by repeated in vivo labeling with DFP32 and the endotoxin test for evaluating the availability of the granulocyte reserve. The effect of steroid treatment on the recovery of the granulopoiesis has been studied with autotransfusions of in vitro DFP32 labeled granulocytes in the same subject and performed before, during and after the treatment was discontinued.

The following conclusions have been reached:

1. The efficiency of the granulopoiesis is based upon the availability of the bone marrow granulocyte reserve.

2. The bone marrow granulocyte mobilization with endotoxin and the in vivo granulocyte labeling with DFP32 give an evaluable information about the bone marrow granulocyte reserve.

3. The granulocytopenia due to antiblastic therapy corresponds to a depletion of the bone marrow granulocyte reserve.

4. The recovery of a “normal granulocyte count” preceeds the rebuilt of a “normal availability” of the bone marrow granulocyte reserve.

5. The recovery of the blood granulocyte count after prednison is not associated with any favourable change of the granulopoiesis.

Nineteen variants of the iron-binding protein, transferrin, have been described in human serum. The world literature on the distribution of these variants in human populations is surveyed in comprehensive tables and attention is drawn to some of the outstanding deficiencies in our present knowledge of this distribution. It is pointed out that transferrin variants are important markers in anthropological studies.

A multiple birth frequency of 5.59% has been found in 25 Klinefelter sibships, which is statistically significantly higher than expected (P < 0.001).

A family investigation of a patient with Klinefelter's syndrome, who is a triplet himself, revealed 5 twin births and 2 triplet births in three generations.

The mortality of the 19 children from the 9 multiple births born in the 25 Klinefelter sibships was 53% up to the age of 3. Such a high mortality indicates that some of the twins and triplet births might have suffered from chromosome disorders contributing to the high mortality.

If the comparatively high frequency of twins in the sibships with Klinefelter's syndrome as well as Turner's syndrome is confirmed by further studies, this will indicate a relation between the cause of sex chromosome non-disjunction and multiple births or between the predisposition to non-disjunction and multiple births.

The Morris syndrome of testicular feminization is described in two brothers. Cytogenetic findings show in both subjects a 46,XY karyotype in most examined metaphases and a 45,XY karyotype (due to a consistent loss of a small acrocentric) in a smaller percentage (respectively 18.7% and 28.5%). The meaning of these findings is discussed.

A follow-up EEG study in 28 cases with closed head injuries, using MZ co-twins as controls, is described. A new concept in EEG analysis is introduced. A combined EEG code and point scale are more effective in discriminating subtle differences between two EEG records. A high concordance was found whether the EEG showed normal or abnormal patterns. Not only the head-injured twins but also the controls showed more abnormalities than in the normal population. Without this check by co-twins the EEG abnormalities could have been taken for persisting signs of the proband injury. It was found, however, in late follow-up that proband twins showed more EEG aberrations and abnormalities than co-twins, but the probands differed already in pre-traumatic mental make-up from their genetically identical controls. Neither differences in mental make-up nor in EEG characteristics showed any statistically significant correlation with the severity of the proband injury. These observations limit the significance of EEG abnormalities in late concussional states.

This study also indicates that there are individually specific EEG patterns, which in health retain their characteristics throughout life. The EEG pattern is therefore concordant in identical twins. Thus, when a twin is influenced by a brain disease or lesion, the co-twin may serve as a biological control in both acute and follow-up studies.

Dermatoglyphics of 81 females with Turner's syndrome are analysed with regard to the cytogenetic findings and they are compared with the data from normal relatives of both sex. The quantitative traits (total ridge count, a-b ridge count, atd angle) are shifted to an elevation of the means. Centric patterns on the hypothenar area as well as a longitudinal alignment of the main lines and transverse creases are found rather frequently. Previous studies are confirmed.

The proliferative characteristics of human acute leukaemia cells are reported and the relationships between the proliferative alterations and differentiation defect of these cells discussed. The proliferative activity of acute leukaemia cells was also studied in relation to cytostatic treatment.

Emphasis is laid on the fact that in all cases of acute leukaemia the characteristic blast cells of the disease do not constitute a homogenous cell population but can be divided into various sub-classes with different kinetic and proliferative characteristics. It is also pointed out that all cytostatic treatment acts on the most actively proliferating classes and only indirectly on the non-proliferating classes.

Finally, the need for more detailed study of DNA synthesis at chromosome and sub-chromosome level for the purpose of more fully understanding the response of leukaemic cells to the various chemiotherapies is underlined.

It was on June 25, 1943 that the world lost a great mind and a great medical scientist, when Dr. Karl Landsteiner succumbed to the effects of a heart attack that had overtaken him two days before while he was actively at work in his laboratory. He had just passed his seventy-fifth birthday of a lifetime devoted to fundamental research. Shortly before his death he had completed the second edition of his classic book, “The Specificity of Serological Reactions”, and he had also published almost 350 scientific papers describing the results of his pioneering investigations. This year is the centenary of the birth of Karl Landsteiner, and it seems fitting at this time to pay tribute to this genius and benefactor of mankind by reviewing some of his great discoveries.

Of Dr. Landsteiner's discoveries, the one that has captivated the popular imagination the most is his discovery of the A-B-O blood groups, frequently called the Landsteiner blood groups in his honor. At the beginning of the present century, it was recognized that bloods from animals of different species could be distinguished from one another by their serological reactions. For this reason, the use of animal blood for transfusions to human beings was abandoned, but the frequent serious reactions that followed transfusions of blood from one human being to another still remained unexplained. Landsteiner then tested the blood of workers in his laboratory by mixing serum taken from one individual with the red cells of others. He found that instead of the weak or negative reactions that might have been expected, in some combinations strong agglutination of the red cells occurred, while in other combinations no effect was apparent.

The mode of action of the alkylating agent Melphalan on Yoshida ascites tumours resistant and sensitive to alkylating agents in rats has been studied. A combination of autoradiography and analytical histochemistry has been used to measure changes in the cell kinetics. The sensitive strain showed a marked fall in mitotic index, build up in G2 and finally interphase death occurring 24-72 hours after treatment. The resistant form showed only slight mitotic inhibition and a possible recovery phase 24-30 hours after treatment, without evidence of cytological damage.

Palm-print and finger-print patterns were studied in a series of 330 patients with congenital heart disease and compared to a control group of 200 patients with acquired heart disease.

156 patiens had associated malformations, while 174 other patients had isolated heart disease. Both groups were studied separately.

Simian creases are more frequent in the malformed patients than in the controls, but the difference is only significant in patients with multiple malformations.

A triradius in the positions t' is seen with a higher frequency in patients with multiple malformations and in patients with isolated heart disease than in the controls. The position t” however is only more frequent in the group of patients with multiple malformations, and tends to be associated more often with a ventricular septal defect and Fallot's tetralogy than with an atrial septum defect, aortic stenosis, coarctation and patent ductus.

Hypothenar patterns are more frequent in patients than in controls.

The results concerning finger-print patterns show a diminished frequency of arches in patients with isolated heart disease compared with controls and patients with multiple malformations. Variations between the different types of congenital heart disease were not important. They are partly in agreement, partly in disagreement with the results of other authors.

21 patients with familial congenital heart disease show an increased frequency of ulnar loops and a low frequency of whorls compared to the rest of patients.

This study does not include classical chromosomal aberrations and no malformation syndromes besides the Holt-Oram syndrome and the supravalvular aortic stenosis syndrome. The first one is characterised by an increased frequency of axial triradius in the t” position and of simian creases, while the second one seems to be without any dermatoglyphic particularity.

The fact that controls as are maintained in most biological experiments, could even be studied ebulliently in human population, by observing a MZ pair, a member of which is exposed to a certain anomaly and the other acts as control, becomes more vivid and recommended from the present studies. For, they can be directly related to human health and welfare.

Permanent changes due to typhoid incidence in physical, mental and anthropometric traits of a member of MZ twin pair may be suggestive of some “beneficial interaction of typhoid bacillus with certain intricate mechanisms like RNA and protein synthesis, as has been envisaged earlier.

Attempts to induce greater relative tumour specificity in cancer chemotherapeutic drugs may be aimed at (1) reducing toxicity towards host tissues or (2) increasing the susceptibility of the tumor.

1. Pretreatment with certain thiol derivatives has some protective action against the host toxicity of X-irradiation and of certain alkylating agents. However, in many cases even better protection against the tumour-inhibitory action occurs so that the therapeutic index is unfavourably affected.

2. Pretreatment with glucose which accentuates the pH difference between normal and tumour tissues can, in some cases, produce an increase in therapeutic index.

3. The most encouraging aspect is to explore and take advantage of biochemical variations from the normal tissue pattern which are found in certain tumours, e.g. the successful treatment of the ADJ/PC5 mouse myeloma with «aniline mustard» is believed to be related to the very high glucuronidase activity of this tumour.

This paper summarizes some studies recently carried out in this Institute in the field of cancer chemotherapy.

Three main groups of data are reported:

a) different sensitivity to chemotherapy of the same tumor transplanted in different sites of the body;

b) a method to study cancer dissemination as a basis for cancer chemotherapy;

c) a system to perfuse tissue culture with the blood of living animals as an approach to study duration of action of antitumoral drugs.