Volume 27, Issue 12

The model of a flip-flop consisting of an interacting pair of completely equivalent chemical reaction systems (branches) is displayed. Beyond a critical threshold value of the influx to the apex substance of both branches the symmetric state (both branches active to an equal extent) is unstable; so essentially only one will be active. A negative pulse in the influx beneath the threshold brings the total system back towards the symmetric state. Introducing additional short reaction chains into both branches that cause a time delay in the rate of destruction of the end products generate an overshoot, so the opposite branch is active, when the pulse is over. Thus the same pulse can switch over the system in either direction opposite to the former state

In a simple two-compartment system, the behaviour of a flip-flop can be obtained by reversible reduction of selective membrane permeability. The behaviour corresponds to a triggerable reversal of “differentiation” of the two-cellular system. The model is identical with the simplest Rashevsky- Turing system, that is a two-compartment system showing spontaneous differentiation if the selective permeability for one constituent is raised above a critical value. The identity is not accidental and can be interpreted as an example of Rosen’s principle of function change. The phenomenon may be used for an empirical test of the Rashevsky-Turing theory of morphogenesis

29 Si-NMR chemical shifts of several trimethylsilylesters of organic and inorganic acids have been measured and are discussed in detail. It is attempted to find a connection between the 29 Sichemical shift of the ester and the acid strength of the starting acids of the esters. Preparation of some new silylesters is described

The 31 P- and 1 H-NMR spectra of PH 3 , PD 3 , P 2 H 4 , P 2 D 4 , P 3 H 5 , and of a mixture of higher phosphanes were investigated at -60° to -93°C. The chemical shifts of the 31 P-spectra were determined against TMS by means of INDOR measurements and converted to the shifts against 85% H 3 PO 4 at 30°C using (CH 3 O) 3 P as an auxiliary substance. By the same method a P 4 O 6 /CS 2 solution was calibrated as a 31 P-low temperature standard. While liquid P 2 H 4 exhibits no remarkable association, it shows an obvious influence on PH 3 dissolved in it. By means of double resonance experiments the equivalency of protons in P 2 H 4 could be demonstrated as well as the AB 2 system expected for P 3 H 5

The IR, Raman and 1 H-NMR-spectra of Hadacidin (N-formyl-N-hydroxylglycine) and its mono alkali salts are reported and discussed in terms of a structure proposal. The acidity constants given in the literature are corrected

Dehydration can proceed according to one (E2) or two (El, ElcB) step mechanisms. In the first case the leaving groups can be abstracted from the cis or trans (syn or anti) position. In order to get insight into the mechanism, the dehydration of 1-butanol, 2-butanol, D,L-erythro- and D,L-threo-2-butanol-3-d 1 as well as the isomerization of 1-butene and cis-2-butene were studied in the temperature range from 250 to 400°C, using microcatalytic and mass-spectrometric techniques. In order to distinguish between cis and trans elimination, erythro- and threo-2-butanol-3-d 1 were studied. Over AlPO 4 , Ba 3 (PO 4 ) 2 and Ca 3 (PO 4 ) 2 a simultaneous trans and cis mechanism was found. The ratio of cis to trans mechanism was calculated to be 85/15 with Ca 3 (PO 4 ) 2 , 70/30 with Ba 3 (PO 4 ) 2 and 45/55 with AlPO 4 . The cis mechanism is highest for Me-O-distances of the catalysts of 2.5 A which coincides practically with the distance between - OH and -H (D) to be eliminated

A new synthesis has been developed for the hitherto unreported 2-substituted-3-oxo-4H-1,4-oxazines 3b-3j via the cyclodehydrohalogenation of N-aryl-N-dichloroacetyl-2-amino-4′-nitroacetophenones in dimethyl sulfoxide with potassium t-butoxide. The structures of all the oxazine derivatives have been verified by IR and NMR spectroscopy and correlations between the structures and spectrographic characteristics have been made. In every case the only tautomer present was the one in which the carbonyl group in position 3 of the oxazine ring existed in the “keto” form. Attempts to extend these cyclic elimination reactions to the synthesis of oxazepines have failed

3.4.5-Trioxo-2.6-di-tert.-butyl-1.2.6-thiadiazin-1-oxide reacts with o-, m- and p-Nitrophenylhydrazine at the center C=O-group to give hydrazones. However, with phenylhydrazine and 2.4-dinitrophenylhydrazine benzoxadiazepines are formed

UV irradiation of 1,3-dimethyluracil in ice-matrix yields four dimeric dimethyluracils (2 c) - (5 c), which could be isolated by preparative thin-layer chromatography. Attemps for structure elucidation of these four dimers by UV, IR, NMR and mass-spectrometric methodes pointed out, that only NMR-spectra give structural evidences; by IR - not by mass-spectra - certain identification of dimers is possible. In accordance with dimeric thymines and dimeric uracils the syn-dimeric dimethyluracils (3 c) and (5 c) are stable in 6 N HCl, the anti-dimers are monomerisized. Investigations of stability in HCl gives informations about structures of cyclobutane pyrimidine dimers

Structures of dimeric dimethyl-uracils have been established by simulation of 90 Mc NMR spectra

Polarization measurements of pheophytin a and b show that the oscillator directions of successive electron transitions are alternating. There are thus 3 transitions in the long wavelength range of the electronic spectrum (at about 15000, 18500 and 19500 cm -1 ). Further electron transitions are indicated by the Soret band. The 0→0 bands are each accompanied by 1-2 vibrational trasitions. The different spectral features of pheophytin b compared to pheophytin a, in the range of 17500 cm -1 to 21000 cm -1 , results from different intensity factors for the equivalent electron transitions

Kinetic studies of the reaction of papain with succinic anhydride demonstrate the reactivity of 10 amino groups, two of which are easily deacylated giving a stable succinylpapain with 3 free amino groups one of which is the free amino group of the terminal isoleucin. This modified enzyme has the tenfold solubility of papain between pH 5,9 - 9 and is a little more sensible to temperature than papain. Kinetic parameters of succinylpapain with N-Benzoyl-ʟ-arginine ethylester are: K m app =1,2 x 10 -2 ᴍ( papain: 1,8 x 10 -2 M) κ cat =505 min -1 (papain: 475 min -1 ) at pH 6,2 and 37°C. The activity with the anionic substrate casein was 120 ± 10%, with the cationic protamine was 200 ± 20% of the activity of papain. Nitration of 17 ± 1 tyrosines of succinylpapain with tetranitromethane has only a limited effect on the activity of the enzyme. The kinetics of this reaction suggests the existence of three groups of tyrosines with different reactivity. The reaction of papain with tetranitromethane gives only insoluble, cross-linked products. Three of five present tryptophanes of papain and succinylpapain are oxidized by N-bromosuccinimide in the native state; in 8 ᴍ urea all residues are accessible. The esterase- and proteolytic activity of the oxidized enzyme decrease to less than 50% of controls while with benzoyl-ᴅ, ʟ-arginine-p-nitro-anilide there was observed an increased activity of about 250%. The stability of the enzyme drops considerably after oxidation of five tryptophane residues. Function and reactivity of the modified amino acids are discussed with regard to the results of the x-ray analysis of the enzyme

The bacteriophage 2C, when stored at 4°C loses its biological activity rapidly. It has been observed that the DNA from such inactive phages is also degraded. The preliminary studies indicate that the “heavy” strand of the DNA gets degraded first followed by the “light” strand

3 H-thymidine incorporation by secondary cultures of embryonic rat cells and by cultures of a permanent rat cell line is strongly inhibited a few minutes after addition of hydroxyurea (HU) to the culture medium (2 × 10 -3 ᴍ and 5 × 10 -4 ᴍ, resp.); normal embryonic rat cells are considerably less sensitive to the drug than are permanent cells. About 76 percent of the population of a secondary culture can be synchronized at the beginning of the S-period, if the cells at first are accumulated in G 1 phase by incubation in serum-free medium and subsequently are stimulated by the addition of ten percent calf serum in the presence of 2 × 10 -3 ᴍ HU. The size of DNA replicated in the presence of HU has been analysed by centrifugation in alkaline sucrose gradients. The results indicate that under these conditions DNA subunits are synthesized with sedimentation coefficients between 21S and 30S. These intermediates cannot be joined together, probably because a ligase is inhibited by HU. Secondary culture incubated in medium-containing 1 × 10 -4 ᴍ HU incorporate twice as much 3 H-thymidine as do control cells in HU-free medium. This is due to an increased number of cells in the S phase, as was shown by autoradiography. The kinetics of thymidine incorporation indicate that the duration of G 1 phase is shortened by small doses of HU

Normal embryonic rat cells, which are synchronized in G 1 phase of their cell cycle, by incubation in serum-free medium contain a DNA fraction with a sedimentation coefficient S 20 between 11 and 12. This double-stranded DNA shows a significantly higher buoyant density in caesiumchloride than does the bulk of cellular DNA, and its replication is not restricted to a distinct part of the S period. The possible role of these DNA subunits in the replication mechanism is discussed

This report concerns the ultraviolet absorption and optical rotatory dispersion (ORD) of DNA and of nucleotides down to 185 mμ. An absorption band (y) at about 195 mμ occurs for all these compounds. Similar studies have been made on histones and nucleohistone. These indicate a strong absorption below 200 mμ due to protein. Consequently, if any native DNA is associated with some amount (2 - 12%) of protein (e.g., histones), the molecular absorption of DNA in the said region becomes masked, and no clear y-maximum due to DNA occurs in the absorption spectrum. The absorption of DNA in the y-band region (ca. 190 mμ) seems to be decreased as a result of DNA-protein interaction. No significant change is observed in the absorption region of DNA at longer wavelengths (250-290 mμ). The y-peak of DNA appears at about 190 mμ on complete removal of proteins. This peak is sharper than the conventional one (x) at 260 mμ and is hyperchromic on denaturation, and involves multiple Cotton effects to any degrees similar to that observed at the second peak (260 mμ). The absorption (also ORD) features of nucleohistone at the x and y wavelengths do not provide similar information (e.g., denaturation artefacts) regarding the structure of the nucleohistone contained DNA which is apparently distinct from the structures of native and partially denatured (denaturation 10%) DNA. The weaker π-π* transition (190 mμ) in the DNA bases is very susceptible to nucleoprotein interaction. This result has been used to explain the influence of nucleoprotein interaction on the configuration of DNA in nucleohistone

1. The carbohydrates were oxidized at a significantly faster rate by the kidney than by the liver slices of uromastix. 2. The amount of oxygen consumed by the liver and kidney slices of uromastix is of the similar magnitude

1. Initial glycogen levels in the liver were found to be significantly higher than in the kidneys of the two species studied. The glycogen levels in kidney were however considerably higher than in some mammalian species. 2. Total reducing capacity, true glucose, saccharoid fraction and titratable acidity increase gradually with concomitant decrease in the glycogen levels when liver and kidney homogenates of uromastix and liver homogenate of varanus were incubated for a period of 4 hours. 3. Total reducing capacity, true glucose and the titratable acidity increase gradually, while the glycogen and the saccharoid fraction remain unchanged when the kidney homogenates of varanus are incubated for 4 hours. 4. Total reducing capacity, true glucose and saccharoid fraction in the blood of uromastix are higher than in varanus. The blood glucose levels in both the species are higher than found in the mammals

Isolated crayfish retinas were perfused with four solutions in which Li + , ΝΗ 4 + , Tris H + and glucose were substituted for the sodium ions in the physiological salt solution. The changes of the extracellularly recorded receptor potential (ReP) evoked by short or long stimuli were measured. The changes in the shape of ReP by test solutions were different for each Na-substitute. For lithium ions as a Na-substitute (Tab. I and Fig. 3) the plateau value he was considerably decreased (to ∼20%) contrary to the peak-amplitude h max which even slightly increased. Ammonium ions show quite a different effect than all the other substitutes. The ReP is decreased strongly and irreversibly (Tab. II and Fig. 4). When Tris (hydroxymethyl-ammoniummethane-hydrochloride) is substituted for Na, h max decreased to about 60 per cent and the plateau is even more reduced (to 20 per cent; Tab. III). Only the recovery-value for h e (50% smaller) is markedly different contrary to our former experiments where choline was used as Na-substitute (decrease 20%). Glucose as a substitute for sodium chloride caused strongly decreased peak-amplitude h max 26% (Tab. IV and Fig. 9). Increased osmotic pressure due to excess glucose causes irreversible damage of the ReP (Tab. V). All the changes except those produced by NH 4 + were reasonably reversible. The results can be explained by the following assumptions: a) the maximum of the ReP is caused mainly by an increase in the permeability of the cell membrane for sodium. Ca- and Mg-ions also contribute to it to a certain degree. b) The plateau value of the ReP to long light stimuli is determined: 1. by the sodium concentration gradient, 2. by active transport processes, 3. by the Ca ++ - and Mg ++ -gradients, 4. the chloride gradient may perhaps contribute to this value

Basic to the proposed therapeutic usage of the difference in the in-vivo proliferation control between cancer and normal cells are the temporary selective increase in the proliferation rate and number of cancer cells in all kinds of tumors but without increase of the proliferative activity of normal cells. To further this aim, measurements of cellular kinetics are used, in connection with the glycolysis of different tumor tissues under saturation conditions, with the relationship between cancer cell cycle and glycolytic rate, or the local glucose level respectively, with the wide range of glucose concentrations in tumor regions which differ the conditions of supply, with the pO 2 -value critical for tumor growth (≈ 0.4 Torr), with the pO 2 -distribution in tumor tissues and the time distribution of cell cycles in human and animal cancerous tissues. From an approximative description of the cytostatic effects in different tumor regions and its validity limits it is estimated that the sensitivity towarts therapy is decreased to as low as one-tenth in poorly supplied tumor regions. These particular fractions of the tumor tissues determine the degree of tumor resistence. Additionally, from these considerations steps can be derived which could be important for multiplying the effect of the cytostatic attack on the critical tumor regions with poor supply conditions. These steps include: a) usage of combinations of cytostatic agents directed against all three sensitive phases of the cell cycle (S-G 2 -M); b) increase in blood glucose concentration to about 300 mg% for an optimum time span prior to the initiation of the main therapeutic process; c) increase in pO 2 of the inspiration air to 320 or 400 Torr and in the degree of pO 2 utilization by the use of specific pharmaceutic agents for the chosen time span preceding the main therapy; d) stimulation of tumor vascularization preceding the main therapy; e) decrease in the fraction of tumor cells utilizing glucose and O 2 as a consequence of a post-therapy treatment 72 hours after the main therapy. The increase in the fraction of cells in a sensitive phase of the cell cycle is reached folowing synchronization after increasing the glucose concentration until saturation of the glycolytic capacity. Reasons are given, why the cytostatic attack has to be supplemented by other selective mechanisms which damage the tumor cell independent of the phase of the cell cycle. Such a mechanism is the lysosomal cytolytic chain reaction. Here, the death of tumor cells occurring during a sensitive phase of the cell cycle as a consequence of the cytostatic attack helps to damage cancer cells which are in the insensitive phase. A further mechanism of this kind is the immunological attack, which is also a component of multi-step cancer therapy