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Showing papers by "University of Freiburg published in 1982"


Journal ArticleDOI
TL;DR: The model reconciles seroepidemiological data linking HSV to human genital cancer with the apparent difficulties in finding HSV DNA by biopsy in genital cancer.

433 citations


Journal ArticleDOI
TL;DR: In this paper, the authors derive localization properties of massive particle states which hold in all models of relativistic quantum theory, including gauge theories, starting from the principle of locality of observables.
Abstract: Starting from the principle of locality of observables we derive localization properties of massive particle states which hold in all models of relativistic quantum theory, including gauge theories. It turns out that particles may always be regarded as well localized distributions of matter, although their mathematical description might require the introduction of non-local (unobservable) fields, which are assigned to infinite string-like regions. In spite of the non-locality of these fields one can show that such particles obey Bose- or Fermi (para) statistics, that to each particle there exists an antiparticle and that collision states of particles exist. A selfcontained exposition of the underlying physical ideas is given in the Introduction, and some perspectives for the structure of field-theoretic models arising from our analysis are discussed in the Conclusions.

391 citations


Journal ArticleDOI
TL;DR: Although all HPV 6‐positive condylomata acuminata analyzed in this study revealed HPV 6 DNA of regular molecular weight, two of the Buschke‐Löwenstein tumors, as well as one of the two positive atypical condylmata of the cervix, contained HPV 7 DNA with a remarkable size hetergeneity, apparently all size classes occurred in a supercoiled form without evidence for integration into host cell DNA.
Abstract: 32P-labelled cloned HPV 6 DNA was used as probe to analyze human genital tumors for DNA sequences homologous to HPV 6 DNA. Ninety three percent of all condylomata acuminata (41 out of 44) were found to harbor HPV 6 DNA. Of the remaining three, one contained HPV 1 DNA. No papillomavirus DNA was identified in the two other tumors. All three invasively growing giant condylomata acuminata (Buschke-Lowenstein tumors) investigated also contained HPV 6 DNA. Two out of six atypical condylomata of the cervix hybridized with HPV 6 DNA under stringent conditions, one only under conditions of low stringency. All DNA preparations from malignant tumors studies (54 cervical carcinomas, 10 penile carcinomas, two vulvar carcinomas) failed to anneal with HPV 6 DNA, even under conditions of low stringency. Although all HPV 6-positive condylomata acuminata analyzed in this study revealed HPV 6 DNA of regular molecular weight (5.1 x 10(6)), two of the Buschke-Lowenstein tumors, as well as one of the two positive atypical condylomata of the cervix, contained HPV 6 DNA with a remarkable size classes occurred in a supercoiled form without evidence for integration into host cell DNA.

321 citations


Journal ArticleDOI
04 Nov 1982-Nature
TL;DR: Evidence of an X-chromosome sequence, defined by its restriction enzyme polymorphism, that is loosely linked to DMD is presented, at a distance of approximately 10 centimorgans, as determined by studies on nine informative families.
Abstract: Duchenne muscular dystrophy (DMD) is one of the most common and serious human X-linked disorders. It occurs at a frequency of up to 1 in 5,000 newborn males in most populations studied, with about one-third of all cases due to new mutations1. The primary biochemical defect remains unknown, and no proven prenatal diagnostic test exists, although raised serum creatine kinase levels act as a somewhat equivocal guide to carrier females2. Previous studies have shown no measurable genetic linkage of the DMD locus with any X-chromosome marker3,4. Therefore, if a cloned sequence of the X chromosome could be used to define the locus, and to provide a closely linked set of markers, it would be of considerable importance in the prediction and prevention of DMD, as well as a step towards identifying the basic biochemical defect causing the disease. We present here evidence of an X-chromosome sequence, defined by its restriction enzyme polymorphism, that is loosely linked to DMD, at a distance of approximately 10 centimorgans, as determined by studies on nine informative families. The polymorphism occurs in 29% of women in a control London population and in 22% of carriers for DMD. The linkage data support cytogenetic evidence that DMD is on the short arm of the X chromosome. The object of this letter is to encourage others to make use of our probe, which seems to be linked to the DMD locus.

305 citations


Journal ArticleDOI
TL;DR: In this paper, for two p-dimensional random vectors X and Y with dispersion matrices Σ11 and Σ22, respectively, it is shown that the covariance matrix Ψ 0 of X and y that minimizes the L 2 distance between them can be obtained.

279 citations


Journal ArticleDOI
TL;DR: The tested predictions of the Rabl-model support small time-dependent changes of the nuclear space occupied by single chromosomes and of their relative positions in the interphase nucleus seem possible, while the territorial organization of interphase chromosomes and their arrangement in general is maintained during interphase.
Abstract: In 1885 Carl Rabl published his theory on the internal structure of the interphase nucleus We have tested two predictions of this theory in fibroblasts grown in vitro from a female Chinese hamster, namely (1) the Rabl-orientation of interphase chromosomes and (2) the stability of the chromosome arrangement established in telophase throughout the subsequent interphase Tests were carried out by premature chromosome condensation (PCC) and laser-UV-microirradiation of the interphase nucleus Rabl-orientation of chromosomes was observed in G1 PCCs and G2 PCCs The cell nucleus was microirradiated in G1 at one or two sites and pulse-labelled with 3H-thymidine for 2h Cells were processed for autoradiography either immediately thereafter or after an additional growth period of 10 to 60h Autoradiographs show unscheduled DNA synthesis (UDS) in the microirradiated nuclear part(s) The distribution of labelled chromatin was evaluated in autoradiographs from 1035 cells after microirradiation of a single nuclear site and from 253 cells after microirradiation of two sites After 30 to 60h postincubation the labelled regions still appeared coherent although the average size of the labelled nuclear area fr increased from 142% (0h) to 265% (60h) The relative distance dr, ie the distance between two microirradiated sites divided by the diameter of the whole nucleus, showed a slight decrease with increasing incubation time Nine metaphase figures were evaluated for UDS-label after microirradiation of the nuclear edge in G1 An average of 43 chromosomes per cell were labelled Several chromosomes showed joint labelling of both distal chromosome arms including the telomeres, while the centromeric region was free from label This label pattern is interpreted as the result of a V-shaped orientation of these particular chromosomes in the interphase nucleus with their telomeric regions close to each other at the nuclear edge Our data support the tested predictions of the Rabl-model Small time-dependent changes of the nuclear space occupied by single chromosomes and of their relative positions in the interphase nucleus seem possible, while the territorial organization of interphase chromosomes and their arrangement in general is maintained during interphase The present limitations of the methods used for this study are discussed

279 citations


Journal ArticleDOI
TL;DR: This study provides evidence that the formation of ‘extra MII’ is caused by a shift of the MI/II equilibrium due to rapid binding of the G-protein to MII.

250 citations


Journal ArticleDOI
TL;DR: In this paper, die Darstellung einer Reihe von 3,4,9,10-Perylentetracarbonsaurediimiden 1 wird beschrieben und deren Lichtechtheit quantitativ untersucht and diskutiert.
Abstract: Die Darstellung einer Reihe von 3,4,9,10-Perylentetracarbonsaurediimiden 1 wird beschrieben und deren Lichtechtheit quantitativ untersucht und diskutiert. Es las sich zeigen, das durch Einfuhrung von tert-Butyl-Substituenten die als sehr schwerloslich bekannten Perylen-Pigmentfarbstoffe in organischen Solventien leicht loslich werden und mit hohen Quantenausbeuten fluoreszieren.

197 citations


Journal ArticleDOI
TL;DR: The phosphorylation sites of simian virus 40 large T antigen were determined within the primary structure of the molecule and clustering within two separate regions might correlate with structural and functional domains of this protein.
Abstract: The phosphorylation sites of simian virus 40 large T antigen were determined within the primary structure of the molecule. Exhaustive digestion of (32)P-labeled large T antigen with trypsin generated six major phosphopeptides which could be separated in a newly developed isobutyric acid-containing chromatography system. By partial tryptic digestion, large T antigen was cleaved into an amino-terminal fragment of 17,000 daltons and overlapping fragments from the carboxy-terminal region ranging in size between 71,000 and 13,000 daltons. The location of the phosphopeptides was then determined by fingerprint analyses of individual fragments. Their physical properties were analyzed by sizing on polyacrylamide gels and by sequential digestion and peptide mapping; their amino acid composition was determined by differential labeling with various amino acids. The amino-terminal 17,000-dalton fragment gave rise to only one phosphopeptide (phosphopeptide 3) that contained half of the phosphate label incorporated into large T antigen. It contained phosphoserine and phosphothreonine sites, all of which were clustered within a small segment between Cys(105) and Lys(127). This segment contained five serines and two threonines. Among these, Ser(106), Ser(123), and Thr(124) were identified as phosphorylated residues; in addition, either one or both of Ser(111) and Ser(112) were phosphorylated. The neighboring residues, Ser(123) and Thr(124), were found in three different phosphorylation states in that either Ser(123) or Thr(124) or both were phosphorylated. Phosphopeptides 1, 2, 4, 5, and 6 were all derived from a single fragment extending 26,000 daltons upstream from the carboxy terminus of large T antigen. Phosphopeptide 6 was identical with the previously determined phosphothreonine peptide phosphorylated at Thr(701). Phosphopeptides 1, 2, 4, and 5 contained only serine-bound phosphate. Phosphopeptides 1, 2, and 4 represented overlapping peptides, all of which were phosphorylated at Ser(639) located next to a cluster of six acidic residues. In phosphopeptide 5, a large peptide ranging from Asn(653) to Arg(691), at least two of seven serines were phosphorylated. Thus, large T antigen contains at least eight phosphorylation sites. Their clustering within two separate regions might correlate with structural and functional domains of this protein.

175 citations


Journal ArticleDOI
19 Aug 1982-Nature
TL;DR: The monoclonal antibody inhibited erythrocyte adherence, attachment to glass and gliding motility of M. pneumoniae and localized the adhesin at the surface of the tip structure.
Abstract: The human respiratory pathogen Mycoplasma pneumoniae has several peculiar properties: despite its diminutive size1 it possesses a specialized tip structure2–4; it is motile and glides with considerable speed along inert surfaces5,6, and it exhibits strong attachment to animal cells7 and to inert surfaces8. The latter property is a prerequisite for the survival of this obligate parasite in the host organism. Experimental evidence9–12 suggested that the binding site(s) mediating attachment of the pathogen is a protein, but so far this substance has not been characterized, nor has it been localized in the cell. By using a monoclonal antibody we have been able to localize the adhesin at the surface of the tip structure; it was identified by autoradiography as a protein of molecular weight (Mr) 160,000–190,000. We report that the monoclonal antibody inhibited erythrocyte adherence, attachment to glass and gliding motility of M. pneumoniae.

173 citations


Journal ArticleDOI
TL;DR: The data strongly argue against somatic pairing as a regular event, and suggest a considerable variability of chromosome positions in different nuclei, however, present data do not exclude the possibility of certain non-random chromosomal arrangements in CHL-nuclei.
Abstract: Unsynchronized cells of an essentially diploid strain of female Chinese hamster cells derived from lung tissue (CHL) were laser-UV-microirradiated (λ=257 nm) in the nucleus either at its central part or at its periphery. After 7–9 h postincubation with 0.5 mM caffeine, chromosome preparations were made in situ. Twenty-one and 29 metaphase spreads, respectively, with partial chromosome shattering (PCS) obtained after micro-irradiation at these two nuclear sites, were Q-banded and analyzed in detail. A positive correlation was observed between the frequency of damage of chromosomes and both their DNA content and length at metaphase. No significant difference was observed between the frequencies of damage obtained for individual chromosomes at either site of microirradiation. The frequency of joint damage of homologous chromosomes was low as compared to nonhomologous ones. Considerable variation was noted in different cells in the combinations of jointly shattered chromosomes. Evidence which justifies an interpretation of these data in terms of an interphase arrangement of chromosome territories is discussed. Our data strongly argue against somatic pairing as a regular event, and suggest a considerable variability of chromosome positions in different nuclei. However, present data do not exclude the possibility of certain non-random chromosomal arrangements in CHL-nuclei. The interphase chromosome distribution revealed by these experiments is compared with centromere-centromere, centromere-center and angle analyses of metaphase spreads and the relationship between interphase and metaphase arrangements of chromosomes is discussed.

Journal ArticleDOI
TL;DR: It is proposed that muscle co-activation recorded in spastic children is due to an impaired maturation of the locomotor pattern with an early neuronal adaptation to altered muscle fibre mechanical characteristics.

Journal ArticleDOI
TL;DR: Analysis of the Jijoye (EBV) genome with cloned M-ABA ( EBV) probes specific for the sequences missing in P3HR-1 virus revealed that the sequences of M- aBA (EBv) BamHI-H2 are not represented in JijoyE (EB V).
Abstract: The nontransforming Epstein-Barr virus (EBV) strain P3HR-1 is known to have a deletion of sequences of the long unique region adjacent to the large internal repeats. The deleted region is believed to be required for initiation of transformation. To establish a more detailed map of the deletion in P3HR-1 virus, SalI-A of the transforming strain M-ABA and of P3HR-1 virus was cloned into the cosmid vector pHC79 and multiplied in Escherichia coli. The cleavage sites for BamHI, BglII, EcoRI, PstI, SacI, SacII, and XhoI were determined in the recombinant plasmid clones. Analysis of the boundary between large internal repeats and the long unique region showed that in M-ABA (EBV) the transition is different from that in B95-8 virus. The map established for SalI-A of P3HR-1 virus revealed that, in contrast to previous reports, the deletion has a size of 6.5 kilobase pairs. It involves the junction between large internal repeats and the long unique region and includes more than half of the rightmost large internal repeat. The site of the deletion in the long unique region is located between a SacI and a SacII site, about 200 base pairs apart from each other. The sequences neighboring the deletion in the long unique region showed homology to the nonrepeated sequences of the DSR (duplicated sequence, right) region. Sequences of the large internal repeat are thus fused to sequences of the DSL (duplicated sequence, left) region in P3HR-1 virus DNA under elimination of the DSL repeats. Jijoye, the parental Burkitt lymphoma cell line from which the P3HR-1 line is derived by single-cell cloning, is known to produce a transforming virus. Analysis of the Jijoye (EBV) genome with cloned M-ABA (EBV) probes specific for the sequences missing in P3HR-1 virus revealed that the sequences of M-ABA (EBV) BamHI-H2 are not represented in Jijoye (EBV). In Jijoye (EBV) the complete DSL region including the DSL repeats is, however, conserved. Further analysis of Jijoye (EBV) and of Jijoye virustransformed cell lines will be helpful to narrow down the region required for transformation.

Journal ArticleDOI
TL;DR: In this article, an overview of the theory of photoelectron angular distributions for atoms is presented, which are embodied in a single asymmetry parameter in the electric dipole approximation, and examined within the framework of the angular momentum transfer formulation.
Abstract: An overview of the theory of photoelectron angular distributions for atoms is presented. Its features, which are embodied in a single asymmetry parameter $\ensuremath{\beta}$ in the electric dipole approximation, are examined within the framework of the angular momentum transfer formulation. The $\ensuremath{\beta}$ parameter is in principle always energy dependent. Within the $\mathrm{LS}$ coupling approximation, however, there are instances, each representing a multitude of particular photoionization processes, in which $\ensuremath{\beta}$ is an analytically determined constant. The energy dependence of the $\ensuremath{\beta}$ parameters in such instances is due entirely to spin-orbit and other relativistic interactions. The study of the energy dependence of the $\ensuremath{\beta}$ parameter in these cases is thus of interest because it spotlights weak-interaction effects which are usually overwhelmed by stronger interactions. We illustrate the general predictions by a detailed consideration of the energy dependence of the $\ensuremath{\beta}$ parameter for $s$-subshell photoionization processes. It is shown that the asymmetry parameters for atomic $s$ subshells are particularly suitable for distinguishing between purely geometrical effects on the photoelectron angular distribution, resulting from physical conservation laws, and dynamical effects arising from relativistic interactions and electron exchange and correlation. In general, the $\ensuremath{\beta}$ parameters for $s$ subshells vary with energy; such variation is largest near minima in the cross sections for the corresponding photoelectron channels and in the vicinity of resonances. However, a number of atomic photoionization transitions are identified for which $\ensuremath{\beta}$ would be a constant (equal to one of the three values 2, $\frac{1}{5}$, or - 1) were it not for relativistic interactions and (in some cases) final-state interchannel coupling and/or initial-state electron correlations. Measurement or calculation of the $\ensuremath{\beta}$ parameters for such transitions thus provides a sensitive measure of the strength of relativistic interactions as well as of electron correlations.

Journal ArticleDOI
TL;DR: The oxidation-reduction potentials involved in the transfer are such that the process may be important in the mode of action of enzymes such as high-potential copper proteins and peroxidases, and perhaps also in the Mode of Action of other proteins if the environment is suitable.

Journal ArticleDOI
TL;DR: In this article, the authors reported evidence for the presence of two carboxylic acid residues being protonated and redeprotonated during the photocycle of bacteriorhodopsin.

Journal ArticleDOI
TL;DR: It is concluded that blood-borne angiotensin II induces vasopressin release by acting on the subfornical organ; depending on the dose of isoprenaline, activation of the endogenous renin-angiotens in system may mediate isopremaline-induced vasoppressin release.

Journal ArticleDOI
TL;DR: Photoaffinity labelling of a membrane subfraction predominantly composed of bile canalicular membranes by the photolabile derivatives of the conjugated bile salts showed covalent incorporation of radioactivity into polypeptides of the same apparent molecular weights as with the subfractions enriched with the sinusoidal membranes.
Abstract: 1 Photoaffinity labelling of a subfraction of plasma membranes of rat liver, enriched with sinusoidal surfaces, with the sodium salts of (3β-azido-7α, 12α-dihydroxy-5β-cholan-24-oyl)-2-amino[2-3H(N)]ethanesuifonic acid, (7, 7-azo-3α, 12α-dihydroxy-5β-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid and (11ξ-azido-12-oxo-3α, 7α-dihydroxy-5β-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid resulted with each derivative in a clear covalent incorporation of radioactivity into polypeptides with the apparent molecular weights of 67000, 52000, 48000, 43000 and about 20000. 2 Photoaffinity labelling of a membrane subfraction predominantly composed of bile canalicular membranes by the photolabile derivatives of the conjugated bile salts also showed covalent incorporation of radioactivity into polypeptides of the same apparent molecular weights as with the subfraction enriched with the sinusoidal membranes. 3 The extent of photoaffinity labelling of the different membrane polypeptides is dependent upon the photolabile bile-salt derivative used. However, with each of the photolabile derivatives the relative ratio of the labelling of the different membrane polypeptides was similar for both membrane subfractions. Provided that the uptake as well as the secretion of bile salts by hepatocytes are carrier-mediated processes, this suggests the participation of the same polypeptides in both processes.

Journal ArticleDOI
15 Apr 1982
TL;DR: In this paper, the crystal structures and phase transitions in fluoranthenyl radical cation salts are reported. Butler et al. used cyclic voltammetry and chronoamperometry to study the electrochemical production of these cation radical crystals of the type (A2), where A was either fluoranthene or perylene and X is PF6.
Abstract: Crystal structures and phase transitions in fluoranthenyl radical cation salts, a new family of organic conductors are reported. The metal to semiconductor transition which is observed seems to be related to a distortion of the stacks of aromatic molecules perpendicular to the stacking direction. Cyclic voltammetry and chronoamperometry were employed to study the electrochemical production of these cation radical crystals of the type (A2)⊚⊕X⊖, where A was either fluoranthene or perylene and X is PF6. It appears that following the initial oxidation of A at the electrode a dimer radical cation is formed. This species then complexes with the anion to give the species of the proper stoichiometry from which the crystals grow. The crystals growing on the anode function directly as electrodes.

Journal ArticleDOI
TL;DR: HPV 1-induced lesions represented typical myrmecia warts, varying in the number and shape of inclusion bodies, while HPV 1 and HPV 2 induced warts was more heterogenous.

Journal ArticleDOI
TL;DR: Cytoplasmic streaming in follicles of Drosophila has been analysed in vitro by means of time-lapse films and follicles which were cultured in vitro for the same length of time as follicle which were filmed developed normally in vivo after injection into a host fly.
Abstract: SUMMARY Cytoplasmic streaming in follicles of Drosophila has been analysed in vitro by means of time-lapse films. Late vitellogenic follicles develop normally in vitro as judged by morphological criteria. Furthermore, follicles (stage 10 and younger) which were cultured in vitro for the same length of time as follicles which were filmed, developed normally in vivo after injection into a host fly. The recorded cytoplasmic movements are, therefore, unlikely to be an in vitro artefact. At early vitellogenic stages (up to stage 9; King, 1970) no cytoplasmic streaming can be detected, but at stage 10A cytoplasmic movements are initiated within the oocyte. At stage 10B, when the nurse cells start degenerating, nurse cell cytoplasm can be seen to flow into the growing oocyte. At stage 11 a central stream of nurse-cell cytoplasm reaches the oocyte within a minute. The ooplasmic streaming is most rapid at stage 10B and stage 11 and only an oocyte cortex up to 7 /tm thick remains stationary. Once the bulk of the nurse-cell cytoplasm has poured into the oocyte (stage 12) the cytoplasmic movement ceases, first in the nurse cells and later in the ooplasm. In mature oocytes no cytoplasmic streaming can be detected.

Journal ArticleDOI
TL;DR: In this paper, an efficient intramolecular transfer of electron deficiency from tryptophan (TrpH) to tyrosine (TyrOH) was observed in numerous synthetic and natural peptides in aqueous solutions.

Journal ArticleDOI
TL;DR: Under the conditions employed, it appears that deposits can be formed directly at the subepithelial locus but that complexes are also formed subendothelially, dissociating into free molecules or small complexes and then migrating through the lamina densa and reforming.

Journal ArticleDOI
TL;DR: The results show that the dopamine receptor agonist apomorphine and three antagonists are unable to distinguish between the presynaptic, release-inhibiting dopamine autoreceptors and those postsynaptic dopamine receptors which, when activated, depress the release of acetylcholine.

Journal ArticleDOI
TL;DR: It is hypothesized that the clinical picture is the consequence of chromosome breakage within the Aicardi locus, and unusual X-inactivation patterns in blood and fibroblasts of this patient can be explained by somatic selection against cells with the AICardi phenotype.
Abstract: Aicardi's syndrome, which is characterized by agenesis of the corpus callosum, specific chorioretinal abnormalities, and defects of vertebrae and ribs, is considered a probable X-linked dominant trait with male lethality. All features of this syndrome were seen in a girl with a de novo balanced X/3 translocation (46,X,t(X;3)(p22;q12)). It is hypothesized that the clinical picture is the consequence of chromosome breakage within the Aicardi locus. Then, unusual X-inactivation patterns in blood and fibroblasts of this patient can be explained by somatic selection against cells with the Aicardi phenotype.

Journal ArticleDOI
15 Jul 1982-Cancer
TL;DR: The question of whether grade I prostatic carcinoma patients with early clinical stages benefit from therapy is discussed, and the possibility of reducing the prognosis of patients is not reduced in comparison to that of healthy males of the same age.
Abstract: A new histologic grading system for prostatic adenocarcinomas is presented, and its clinical significance tested. Histologic growth patterns and nuclear anaplasia found therein are evaluated independently of each other. The diagnostic categories are in accordance with the histologic classification recently published by the WHO.29 The tumor is denominated according to the least differentiated fraction. Three grades of malignancy, which correspond to significantly different survival probabilities, are distinguished. The prognosis of grade 1 patients is not reduced in comparison to that of healthy males of the same age. Grade 1 patients did not reveal metastases. The rate of tumor-specific deaths increases with the malignancy grade of the tumor. Interobserver reproducibility of this grading is found to be 91%. With 5% undergradings, the representativity is found to be satisfactory. Prostatic carcinomas tend to change their malignancy grades in time. The question of whether grade I prostatic carcinoma patients with early clinical stages benefit from therapy is discussed.

Journal ArticleDOI
TL;DR: Findings indicate that endogenous prostanoids formed in mouse brain during convulsions might possess anticonvulsive properties.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the spread behavior of CH 3 − (CH 2 ) m −1 − CC − cC − C ǫ − C n − COOH with m = 10, n = 8; m = 16, n.2 and m = 0.

Journal ArticleDOI
30 Oct 1982-Virology
TL;DR: In this paper, neutral red or ultraviolet inactivated herpes simplex virus type 1 proved to be mutagenic when infecting cells of the human rhabdomyosarcoma line RD-176.

Journal ArticleDOI
TL;DR: Calculated cycling rates showed that during a normal feeding rhythm the periportal zone should catalyze net glucose output and the perivenous zone should mediate net glucose uptake, as proposed by the model of 'metabolic zonation'.
Abstract: Periportal and perivenous hepatocytes contain different activities (V) of antagonistic key enzymes such as glucokinase and glucose-6-phosphatase. In order to get an insight into the metabolism of the periportal and perivenous area the flux rates (v) of the glucose/glucose-6-phosphate cycle were calculated on the basis of the Michaelis-Menten equation using the measured zonal concentrations of glucose and glucose 6-phosphate, the zonal activities of glucokinase and glucose-6-phosphatase previously reported and the half-saturating substrate con- centrations (Km) of the two enzymes found in the literature. The concentrations of glucose were obtained as a first approximation by measuring the concentrations in portal (= periportal) and hepatovenous (= perivenous) blood; those of glucose 6-phosphate were calculated from the levels determined in microdissected periportal and perivenous liver tissue. The calculations showed (a) that the overall cycling rates agreed remarkably well with those reported for intact animals and (b) that during a normal feeding rhythm the periportal zone should catalyze net glucose output and the perivenous zone should mediate net glucose uptake, as proposed by the model of ‘metabolic zonation’.