[Kidney renin-angiotensin system and water intake].

The authors make a review and critical evaluation of the accumulated experimental material for clarifying the question: whether drinking is physiological process due to exogenously administered angiotensin II (A-II) or to endogenous stimulation of the rena renin-angiotensin system (RAS). There is a parallel between water intake and plasma renin activity (PRA) in states like hypovolemia, hemorrhagia, hypotension, sodium loss, etc. They find sensitivity of some cerebral structures without blood-brain barrier to physiological concentations of A-II. Water intake is increased after venous administration of angiotensin-II within physiological concentrations. It is shown at the same time that central blockade of A-II does not inhibit drinking after water abstention. The authors discover that some effects, leading to an increased water intake, are not due to RAS. Nephrectomy does not alter circadian thythm of drinking of water. They discuss contradiction in experimental data and make an inference that renal RAS could not be considered as a single and sufficient factor for regulation of water intake.


[Degeneration and regeneration of sensory nerve fibers and their endings (receptors)].

After cutting a nerve, inervating a certain part of the body/its nerve fibers and their terminals (receptors) undergo degeneration, which continues several days and proceeds in some of them unevenly quickly. They recover (regenerate) to their normal state and structure several months after the occurred complete destruction of the nervous fibers and terminals. The author describes the results from studies on the inervation of skin transplants and scars in experimental animals and persons to clarify the question about the origin of the regeneration nerve fibers--whether by growth of the central part of the cut nerve or by formation of this part independently in an area. The finding of capsulated receptors--the bodies of Meissner and bulbs with dense vindingsin 2 to 16-years old scars is a sure proof that regenerated nerve fibers and their terminals originate by growth from those cut at the surface of the grafting of the transplant e.g. from the central.


[Brain catecholamines, mental diseases, aging and senile dementia: biochemical and pharmacological aspects].

Catecholamines (CA) are among the most well known neurotransmitters (NT) which act in a wide range of brain structures and are involved in many important functions, such as general arousal, autonomic, neuroendocrine and motor control and possible in emotion and mentation. The neuropharmacology of the brain CA synapses has played a crucial role in understanding the complex phenomena of the central neurotransmission and the feed-back mechanisms by which the central neurones adapt optimally to the functional needs at any time. The model of neurotransmission, as well as the mechanism by which various substances act at the synaptic level are briefly outlined. Due to the fact that the CA are implicated in many important functions of the brain, it has been suggested that certain mental diseases such as depression, as well as mental and behavioral manifestations of the ageing brain might have their origin in an impairment and particularly in a functional deficiency of the CA occurring at various structures. The available evidence in support to this view is outlined and the hypothesis that senile mental deterioration and the mental impairment encountered in various types of dementia (senile, presenile and multi-infarct) may be due to deficiency of the brain CA is discussed. Since the CA and particularly the dopamine deficiency seems to be a common denominator in depression and in senile mental deterioration, it is suggested that the dopaminergic drugs may serve as useful therapeutic means on one hand and important tools for testing the validity of the above hypotheses on the other.


Estimation of 5 alpha-dihydrotestosterone receptors in human breast tumors by the immobilized antibody method.

A simple method for estimation of 5 alpha-dihydrotestosterone (DHT) receptors in the cytosol of human breast tumors is described. It is based on the competition of immobilized antibody with the receptors for the labeled hormone. Out of eleven patients with primary breast tumors, four had DHT-receptors, three were negative, and four patients were border line cases.


Escherichia coli tRNA (uracil-5-)-methyltransferase: Inhibition by analogues of adenosylhomocysteine.

Structural analogues of adenosylhomocysteine (AdoHcy) have been tested as inhibitors of a tRNA(uracil-5-)-methyltransferase preparation obtained from Escherichia coli. All analogues tested gave linear competitive inhibition kinetics with adenosylmethionine (AdoMet) as the variable substrate. Comparison of the Ki values obtained leads to the following conclusions concerning the specificity of the AdoMet-AdoHcy binding site on the enzyme: (i) the terminal amino group of the amino acid moiety is necessary for activity; (ii) both a chiral change of the asymmetric carbon atom of homocysteine and the presence of the terminal carboxyl group contribute little towards inhibitory activity; (iii) analogues in which the amino function of the adenyl moiety is modified or substituted are still potent inhibitors; (iv) inhibitor specificity is considerably reduced when adenine is replaced by a pyrimidine base.


Identity of malonyl and palmitoyl transferase of fatty acid synthetase from yeast. Functional interrelationships between the acyl transferases.

Functional interrelationships between the acyl transferases of yeast fatty acid synthetase were investigated. In binding assays with synthetase modified by 5,5'-dithiobis(2-nitrobenzoic acid), 4--5 malonyl transferase entities per multienzyme complex molecule could be titrated. In the presence of palmitoyl-CoA these malonyl transferases were found inaccessible to malonyl-CoA, whereas the acetyl transferases were reactive towards acetyl-CoA. Between four and five palmitoyl transferase entities per synthetase equivalent were found reactive towards palmitoyl-CoA, the palmitoyl binding being inhibited by malonyl-CoA. Following palmitoyl binding the acetyl transferases were found towards acetyl-CoA. Substrate model assays were consistent with these data. It is concluded that malonyl and palmitoyl transferases are closely coupled enzyme components of the multienzyme complex which are fairly independent of the acetyl transferase entities. The molecular basis for the observed coupling will be given in the following paper.


Identity of malonyl and palmitoyl transferase of fatty acid synthetase from yeast. 2. A comparison of active-site peptides.

Active-site peptides of malonyl and palmitoyl transferase from yeast fatty acid synthetase were isolated and sequenced to try to prove the hypothesis [J. Ayling, R. Pirson & F. Lynen (1979) Biochemistry 11, 526--533] that both enzymes are identical. For this purpose synthetase modified with 5,5'-dithiobis(2-nitrobenzoic acid) was labelled with either [14C]malonyl or [14C]palmitoyl residues followed by proteolytic digestion of the labelled protein. [14C]Malonyl-peptides were isolated by conventional purification procedures; their structures were determined by a combination of methods. [14C]Palmitoyl-peptide material was purified by high-performance liquid chromatography and the structure determined by solid-phase Edman degradation and other analytical methods. Serine was identified as the acyl acceptor group in both transferases. Comparison of the sequence data available shows that the sequence around the acyl acceptor group in both cases is identical. This proves the identity of malonyl and palmitoyl transferase.


Interaction of arginine with the ribosomal peptidyl transferase centre.

Arginine inhibits the formation of acetylleucyl-puromycin from C(U)-A-C-C-A-LeuAc and puromycin ('fragment reaction'), catalized by Escherichia coli and yeast ribosomes. From 18 different L-amino acids assayed, arginine was the most effective in producing inhibition (50% inhibition at 20 mM, with 1 mM puromycin). L-Argininamide and D-arginine gave about the same inhibition as L-arginine. The inhibition by L-arginine is competitive with respect to puromycin. The plot of the slopes obtained in a Lineweaver and Burk representation versus [Arg]2, and the plot of 1/v versus [Arg]2 at a fixed concentration of puromycin, are linear, which seems to indicate that two arginine molecules must interact at the puromycin binding site to produce inhibition. In addition to the 'fragment reaction', arginine inhibits the non-enzymatic binding of AcPhe-tRNA, C(U)-A-C-C-A-Leu and C(U)-A-C-C-A-LeuAc to ribosomes. However, it does not inhibit poly(U)-directed polyphenylalanine synthesis or the reaction of puromycin with AcPhe-tRNA previously bound to the peptidyl site. The results agree with arginine binding to the acceptor site, and with a sequential mechanism for the 'fragment reaction', puromycin binding first.


The identification of apocytochrome b as a mitochondrial gene product and immunological evidence for altered apocytochrome b in yeast strains having mutations in the COB region of mitochondrial DNA.

The yeast mitochondrial translation product of Mr 30 000 is identical with apocytochrome b. After labelling in vivo with [35S]sulphate in the presence of cycloheximide, the radioactivity in this product present in solubilized submitochondrial particles, was completely recovered in pure cytochrome bc1 complex as a single polypeptide. We show that this translation product is identical with apocytochrome b using peptide mapping by limited proteolysis according to Cleveland et al. [J. Biol. Chem. 250 (1977) 8236-8242] and by immunoprecipitation with a specific antiserum against apocytochrome b. New mitochondrial translation products in 36 strains of Saccharomyces cerevisiae having mutations in the COB region of the mitochondrial DNA, are precipitated by this antiserum. This is consistent with the assumption that many of the cob mutations are localized in the structural gene for apolcytochrome b on mitochondrial DNA.  Mutations in two intervening sequences can give rise to products related to apocytochrome b that are considerably longer than normal apocytochrome b. We discuss the hypothesis that in these mutants splicing of the messenger RNA does not occur correctly and that, as a consequence of this, ribosomes read through in an intervening sequence.


Immunochemical characterization of the basement membrane glycoprotein laminin.

Laminin was recently characterized as being a major non-collageneous protein of the basement membrane matrix produced by a mouse tumor. It was extracted from the tumor matrix with neutral buffer and purified under non-denaturing conditions. Rabbit and guinea pig antisera raised against laminin or a large pepsin fragment P1 of laminin showed strong binding to both laminin and peptide P1 but only a weak reaction with reduced and alkylated laminin. The major antigenic determinants of laminin were located in a disulfide knot, comprising one third of the molecule, which resisted degradation by pepsin or cyanogen bromide. Minor antigenic determinants shared by the native and reduced protein could also be identified. The data were interpreted as showing that laminin consists of conformationally rigid as well as more flexible domains. Absorption studies with mouse kidney homogenate indicated that authenic basement membranes contain a protein immunologically identical to laminin. Tissues from other species contain a related protein which exhibits partial cross-reaction with mouse laminin. Together with immunofluorescence data the findings demonstrate that laminin, like type IV collagen, occurs in most basement membranes of the body.


A novel ATP-driven glucose transport system in Escherichia coli.

In Escherichia coli wild-type cells and in ATPase-deficient cells (unc mutants), glucose was found to be transported mainly by an ATP-driven system. The evidence is based on experiments involving interference at different sites of energy metabolism with the use of uncouplers, arsenate, and starved cells. Furthermore, addition of succinate to starved cells increased glucose uptake only in the wild-type cells, where ATP could be regenerated. Glucose transport was also ATP-dependent in cells deficient in methyl-beta-galactoside transport (a system that carries glucose specificity). It was found to be shock-sensitive in all strains tested. The NOVEL ATP-driven glucose transport is a high-affinity (Km 3-10 microM) and high-capacity (V 240-330 Mmol . min-1 . mg cell protein-1) uptake system.


Mutagenic DNA repair: insertion of nucleotides opposite non-coding template structures by a reversed 3'-5' exonuclease reaction? A hypothesis.

1. The enzymatic mechanism of mutagenic DNA repair is unknown. None of the characterized DNA polymerases is capable of polymerization past non-coding template structures. 2. A hypothesis is proposed according to which polymerization opposite non-coding template structures is catalyzed by the DNA-polymerase-associated 3'-5' exonuclease under conditions which shift the equilibrium of the 3'-5' exonuclease reaction DNAn + H2O in equilibrium DNAn-1 + dNMP to the left, i.e. to the incorporation of deoxynucleoside monophosphates. 3. Conditions which favor the incorporation of dNMP by the reversed 3'-5' exonuclease reaction include a high dNMP concentration, a coupled H2O-consuming reaction and a hydrophobic enzyme environment. 4. The statements of the hypothesis are supported by published work on the biochemistry of DNA polymerases and their associated 3'-5' exonucleases, the genetics of mutagenic DNA repair and the involvement of Escherichia coli DNA polymerase III in this process. 5. The hypothesis offers an explanation of the mutator and antimutator properties of certain genes, in particular of DNA polymerase genes, and also explains how some drugs act mutagenically during DNA replication and antimutagenically against mutagenic DNA repair.


Production of a soluble form of fumarate reductase by multiple gene duplication in Escherichia coli K12.

1. Ampicillin-hyperresistant mutants of Escherichia coli K12 bearing multiple gene duplications in the ampC (beta-lactamase) gene region of the chromosome overproduced at least six proteins with molecular weights 97,000, 80,000, 72,000, 49,000, 33,000 and 26,500 during anaerobic growth. All but two of the proteins (80,000-Mr and 49,000-Mr) were also overproduced during aerobic growth. The distribution of the proteins in soluble and particulate cell fractions was investigated. 2. The 33,000-Mr and 72,000-Mr components were identified as beta-lactamase and the amp-linked frdA gene product, fumarate reductase, respectively. Co-sedimentation of the 26,500-Mr component with the fumarate reductase suggested that the smaller protein could be functionally related to the reductase. The lack of correspondence between the amplified proteins and the products of other amp-linked genes, aspA and mop(groE), indicated that these genes are not included in the repetitive sequence. 3. Fumarate reductase activities were amplified up to 32-fold by the multiple gene duplications. Two forms of fumarate reductase were produced: particulate (membrane-bound) and soluble (cytoplasmic). Production of the soluble form occurred when the binding capacity of the membrane was saturated. Both forms of fumarate reductase were enzymically active but the soluble form was readily inactivated under assay conditions.


Mechanism of action of aminoglycoside antibiotics. Binding studies of tobramycin and its 6'-N-acetyl derivative to the bacterial ribosome and its subunits.

6'-N-[14C]Acetyl-tobramycin and [3H]tobramycin were synthesized and their binding to Escherichia coli ribosomes and ribosomal subunits studied using equilibrium dialysis. THE 70-S ribosome, as well as its 50-S and 30-S subunits, bound tightly to 6'-N-acetyl-tobramycin. The binding of [3H]tobramycin to ribosomes was quite different. The 70-S ribosome was observed to possess several classes of binding sites; of these, one was determined to be of higher affinity and lower capacity, the 6'-N-[14C]acetyl-tobramycin site. The isotopic dilution method was used to define the specificity of the interaction. The selective binding of 6'-N-[14C]acetyl-tobramycin was highly reversible by tobramycin, kanamycins A, B, C and neomycin, but not by streptomycin or erythromycin. Gentamicin C1a was a poor inhibitor. This suggested that either the kanosamin or garosamin rings might be determinant in the binding of these molecules, as well as the 6'-amino group.


Nucleolar DNA organization in the interphase nuclei of mouse fibroblasts.

The organization of nucleolar DNA in interphase nuclei of somatic cells was studied at the ultrastructural level using oxidized DAB as a nucleic acid stain. Some finely filamentous networks of DNA-containing structures were observed within the nucleolar fibrillar component. They originated from the perinucleolar shell of condensed chromatin and from a chromatinic area with a honeycomb like structure. The latter was significantly associated with nucleoli and is believed to be a part of the nucleolar organizer region.


Microfilament-associated proteins in tissue culture cells viewed by stereo immunofluorescence microscopy.

Stereo immunofluorescence microscopy avoids the problem of juxtaposition of structures often encountered in normal fluorescence microscopy. The procedure has been used in conjunction with antibodies against microfilament associated proteins to reveal the arrangement of microfilaments in a rat mammary cell line both in the fully spread state and in cells during the process of spreading on the substratum. use of antibodies to myosin, tropomyosin, alpha-actinin and filamin emphasizes that at early times during the spreading process these proteins are abundantly present underneath the upper plasma membrane, suggesting that the cortical layer present underneath this membrane may be contractile. In addition the results emphasize that even in well spread cells microfilament bundles are expressed both above and below the nucleus, in agreement with the assumption that microfilaments may form a supporting layer underneath the plasma membrane.


Identification of multiple microtubule initiating sites in mouse neuroblastoma cells.

Mouse neuroblastoma N-18 cells can be induced by serum deprivation to sprout multiple neurite-like processes which contain many microtubules. Mitotic drugs such as colcemid and colchicine depolymerize these microtubules and the cells lose their processes. Reappearance of microtubules after removal of the drugs was followed by immunofluorescence microscopy using tubulin specific antibodies. At early recovery times multiple star-like structures which contained tubulin were detected in the perinuclear are and in the cytoplasm of individual cells. The mean number seen per cell as approximately 5. Their formation preceeded the organization of the complex microtubular networks typical of N-18 cells. The probable action of these structures as microtubular organization centers (MTOCs) is discussed. Multiple structures were detected during recovery from the influence of mitotic drugs both in previously induced and non-induced N-18 cells, suggesting that N-18 cells harbour the potential of formation of multiple organization centers even without previous induction. We discuss the possibility that differentiation of neuroblastoma N-18 cells may require microtubular organization centers.


Distribution of molecule numbers per secretion granule. A study of crystals in glucagon secreting cells.

The occurrence of a crystalline component in secretion granules of teleost A-cells (islets of Langerhans) has been used to derive, in Xi-phophorus helleri, the size distribution of secretion granules in terms of (glucagon) molecule numbers. The distribution is asymmetric with the arithmetical mean = 7.1 x 10(5), the median Q0.5 = 4.7 x 10(5), and the range from 8.5 x 10(4) to 4.5 x 10(6) molecules, as determined in a sample of 203 crystals from 9 specimens. This result is based on the following assumptions: The crystals are rhombic dodecahedra with a greater than 4.2 nm and space group P213, thus much resembling cubic porcine glucagon; they are teleost glucagon and contain the whole glucagon content of the granule. If the latter assumptions are rejected, the above molecule numbers become minimum numbers of protein molecules. A change to other space groups also compatible with the diffraction patterns observed would only double the above values. The values are compared with corresponding ones from other species and also from other types of endocrine cells and errors are discussed.


Suspension culture of myocardial cells from newborn rats.

Myocardial cells from newborn rats were held in a spinner type culture for 2 days and then explanted into culture flasks. Three main cell types were observed: single multipolar cells of embryonic type, cell aggregates containing 10 to 50 connected cells, and bipolar cells retaining some adult characteristics. Except for the latter, up to 95% of intact cells settled and were beating 6 hours after explantation. The percentage of fibroblast-like cells was drastically reduced when compared with conventional cultures. Cell debris could be removed 2 hours after explantation by changing the culture medium, or more effectively by a density step centrifugation using Lymphoprep or Lymphoprep-Ficoll mixtures.


Markers for membranous cell components. The 6th International Subcellular Methology Form, Guildford/United Kingdom, 25-28 July 1978.

Problems concerning the use of "markers" in cell fractionation experiments are currently in the forefront in many areas of cellular investigation. Points of view and standards of application vary widely. This report has emerged from a debate during the 6th International Subcellular Methodology Forum, Guildford, U.K., 25-28 July 1978. Marker criteria are discussed, first in a general sense and then in terms of specific cell components. Use of multiple marker criteria is stressed along with selective modulation, cytochemistry, and morphological analyses for fraction identification and evaluations of yield and purity. Finally, some specific recommendations are made toward documentation that journal editors might expect from authors.


Treatment of infantile E. coli gastroenteritis with specific bovine anti-E. coli milk immunoglobulins.

A milk immunoglobulin concentrate (MIC) containing antibodies to enteropathogenic E. coli strains was prepared by hyperimmunisation of pregnant cows and using the milk obtained during the first 6 to 8 days of lactation. The sterile concentrate contained 70 to 80% protein and 35 to 40% immunoglobulin. The antibacterial activity was measured by bacterial passive agglutination, bacteriostatic activity in vitro, phagocytic clearance in vivo, and a protection test in mice. Though differences in titers were observed, adequate immunologic activity was demonstrated by these tests. Clinical studies were performed with 60 patients (aged 10 days to 18 months) suffering from diarrhoea with isolation of enteropathogenic E. coli. They were treated for 10 days with MIC and stool cultures were done prior to, during, and 2, 3 and 4 days after termination of treatment. Among 51 patients infected with E. coli strains incorporated in the vaccine, stool cultures became negative in 43 (84.3%) after treatment with MIC and 8 remained positive. Nine patients infected with strains O 78:K80(B-) and O 114:K--(B-)--which were not included in the vaccine used for immunisation--served as controls. Only one patient in this group became negative. If all patients receiving antibiotics for non intestinal infections during the treatment period are omitted the results remained unaltered: MIC was effective in 32 out of 38 patients (84.2%). These differences were highly significant. These results provide evidence that treatment with specific MIC is effective in eliminating enteropathogenic E. coli from the intestine.


Hypothalamic-pituitary function in the old irregularly cycling rat.

Older irregularly cycling and younger regularly cycling rats exhibited similar increases in LH levels 1, 2 and 3 wks after ovariectomy, but FSH reached higher levels in the older than in the younger rats after ovariectomy. Neither the ability of 5 microgram/kg estrogen to suppress gonadotropin levels nor the capability of larger doses of estrogen (250 micrograms/kg) and/or progesterone (10 mg/kg to trigger an LH release were altered with age. LH release from the pituitary in response to exogenous gonadotropin releasing hormone (GnRH) was attenuated in ovariectomized older rats, but was partially restored after estrogen and/or progesterone priming. The FSH levels after GnRH treatment were greater in the estrogen primed aged that in estrogen-primed younger rats. The disruption of regular cycles in older rats may be due to a lack of a neural signal for gonadotropin release rather than a failure of the hypothalamus to respond to the positive feedback effect of estrogen or the failure of the pituitary to respond to GnRH.


Individual factors influencing the response to a beta-adrenergic blocking agent given alone and in combination with a diuretic on arterial hypertension.

103 patients with arterial hypertension were treated with timolol + placebo for 7 weeks in a multicentre trial, and with timolol + hydrochlorothiazide and amiloride for a further 7-week period. The decrease in blood pressure (BP) produced by timolol alone was influenced neither by the dose of timolol, initial heart rate, magnitude of pretreatment BP nor by age. 64% of the patients less than 40 years of ages, and 48% of the older patients, were well regulated on beta-blocker monotherapy. When the diuretic was given in addition, the BP response in the older age group improved, whereas younger patients showed no change. A significant correlation was found between age or magnitude of untreated BP and the decrease in BP caused by the diuretic. The cardiothoracic ratio increased significantly on timolol alone, whereas no change was found on the combined therapy. Weight changes in the two different treatment periods showed a significant correlation, but they were not related to the observed reduction in BP. The results suggest that in younger patients, beta-blocker therapy is just as effective as a combined treatment with a diuretic, whereas in older patients considerably better regulation is achieved by combined therapy.


Multicentre comparative trial of tienilic acid and hydrochlorothiazide in hypertensive patients.

To compare the clinical and metabolic effects of a new diuretic uricosuric agent, tienilic acid, with those of hydrochlorothiazide, a multicentre double-blind trial was performed in 56 hypertensive patients. Twenty-eight patients were randomly assigned to take tienilic acid and 28 to take hydrochlorothiazide. The diuretic and anti-hypertensive actions of the two compounds were similar. No significant differences were observed between tienilic acid and hydrochlorothiazide in their effects on urinary and serum electrolytes, hepatic and renal function tests, and fasting lipids. The patients who received tienilic acid showed a significant fall in serum uric acid, mediated by the uricosuric effect. The availability of an agent combining diuretic, antihypertensive and hypouricemic effects offers promise in the treatment of arterial hypertension.


H-2 restriction for lymphocyte homing into lymph nodes.

Migratory patterns into lymph nodes of labeled spleen lymphocytes, injected intravenously, showed considerable differences according to the genetic identity or disparity of donor and recipient mice. The use of mice carrying different H-2 haplotypes in the same B 10 background, or, conversely, the same H-2b haplotype in different backgrounds, showed that no homing was observed in the case of complete disparity at the H-2 complex, contrasting with optimal homing in the case of H-2 identity. Homing was not influenced by disparity at the genetic background. Irradiation of recipient mice did not change the results and suggested that no immunological host-vs.-graft reaction was involved in the H-2 restriction observed. The use of donor-recipient pairs carrying recombinant H-2 haplotypes showed that a single H-2 K and/or H-2 D identity allowed almost optimal homing. The results indirectly suggested that an immunological graft-vs.-host reaction was not involved in the phenomenon but rather a positive recognition of H-2 K or H-2 D identity between donor and recipient cells.


The halophilic properties of pyruvate kinase from Vibrio costicola, a moderate halophile.

Pyruvate kinase from Vibrio costicola, a moderate halophile, appears to be adapted to functioning in the presence of salt. Its stability depends on the ionic strength of the medium. The amino acid composition resembles that of other halophilic enzymes. It is proposed that the halophilic pyruvate kinase utilizes preferentially the Mn++ cofactor which forms more stable complexes in the presence of physiological concentrations of salt.


Protective effect of calcium against the verapamil-induced inhibition of ionophore-mediated calcium translocation.

The inhibitory effect of verapamil on A23187-mediated calcium translocation is antagonized in a competitive manner by increasing concentrations of calcium.


Mean cytoplasmic protein concentration of host erythrocytes and the reticulocyte response in Plasmodium berghei infected mice.

The decreasing mean cytoplasmic protein concentration (MPC) of P. berghei host cells is paralled by an increasing parasitemia and percent reticulocyte response. The reticulocyte response parallels the percent parasitemia except during a period of accelerated reticulocytosis noted during the midpoint of the infection at which time the percent reticulocytes increases at a rate more than double the rate of increase of percent parasitemia. Although the reticulocyte population and the host cell population are usually equivalent, the disparity noted suggests the existence of unique characteristics in the reticulocyte response of P. berghei infected mice.


The effect of acidic polysaccharides and prostaglandin-like substances isolated from Propionibacterium acnes on granulocyte chemotaxis.

Three acidic polysaccharide (AP) fractions and the prostaglandin-like substances (PLS) isolated from P. acnes were investigated regarding their chemotactic activities on polymorphonuclear leukocytes. Both AP's and PLS induced a significant chemotatic response, which suggests their involvement in inflammatory acne vulgaris.


Net ATP synthesis by running the red cell calcium pump backwards.

Ca2+ loaded inside-out vesicles from human red blood cells, yielding C2+ into a Ca2+ free medium with 4 mM EGTA, 2 mM ADP and 10 mM phosphate, produced an excess of 14.9 pmoles . min-1 . (mg protein)-1 of ATP compared to controls in which the transmembrane Ca2+ gradient was abolished by the ionophore A 23 187.


From natural fertility to family limitation: the onset of fertility transition in a sample of German villages.

Utilizing data from a sample of German village genealogies, it is possible to document the changes in reproductive patterns on the family level that started to take place in Germany during the nineteenth century and formed the basis for the secular decline in fertility which eventually encompassed the entire country. One striking finding from this study was the substantial diversity among the small sample of villages in terms of the timing of the emergence of family limitation. While couples in all villages who married during the last half of the eighteenth century appeared to be characterized predominantly by natural fertility the emergence of family limitation began as early as the turn of the nineteenth century in some places and as late as the end of the nineteenth century in others. Occupational differentials with respect to family limitation were also examined. There is little evidence that changes in birth spacing played an important part in the initial phase of the fertility trnsition. Rather, the underlying process appears to involve a change from fertility patterns that were characterized by the absence of parity-dependent control to one in which attempts to terminate childbearing in response to the number of children already born becomes widespread.


An experimentally controlled evaluation of the effect of inositol nicotinate upon the digital blood flow in patients with Raynaud's phenomenon.

The vaso-active effects of inositol nicotinate (Hexopal) were investigated in thirty patients with primary and secondary Raynaud's phenomenon using several non-invasive experimental techniques under controlled conditions. The earlier formed impression that this drug requires a prolonged 'build-up' period was confirmed. Recording the time required to induce Raynaud's phenomenon as well as assessments of total and nutrient digital blood flow showed significant beneficial therapeutic effects upon the skin's microcirculation by inositol nicotinate. This study suggests that the therapeutic effect of this drug is not merely due to vasodilation but that other mechanisms such as enhanced fibrinolysis and lowering of serum lipids may play a significant part in its overall effect. Smokers responded slower than non-smokers, but even elderly patients with longstanding vasospastic disease showed measurably improved digital circulation. Unlike some other drugs in this field inositol nicotinate was found to be effective orally and to be devoid of unwanted side-effects. However, in the majority of patients it failed to abolish their increased vascular spasm although it diminished it significantly in most. It appears to be a safe and well tolerated drug, which, together with other symptomatic measures, merits to be used in the management of vasospastic disease of the extremities even in the presence of partial obliteration of the microcirculation.


An investigation of the effect on platelet function of acetylsalicylic acid, dipyridamole and the two drugs in combination in patients with transient attacks of ischaemia.

Twenty patients suffering from transient attacks of ischaemia were studied. Seven received acetylsalicylic acid, six dipyridamole and seven a combination of the two drugs. No significant difference in platelet aggregation was shown in the acute phase between the three treatment groups using an adenosine diphosphate test method. Using Thrombofax platelet substitute, however, a significant difference was seen in all measures. On the seventh day following the ischaemic attack the Thrombofax values returned to normal but, in contrast, Platelet Factor 4 release was increased. Monthly testing of platelet activity during treatment shows that the combination of acetylsalicylic acid with dipyridamole was more effective in bringing about an early inhibition of Platelet Factor 4 release than either agent alone.


A multicentre general practice study of cinnarizine in the treatment of peripheral vascular disease.

A multicentre, double-blind, crossover study monitoring walking distance and symptomatology was set up to compare the efficacy of cinnarizine with that of placebo in the treatment of patients with intermittent claudication. Walking distances were statistically significantly increased by cinnarizine treatment when it was given before placebo. This improvement was maintained without further significant deterioration when the patients were switched to placebo therapy. A smaller but statistically significant increase in walking distance was observed after the first 12 weeks of tarizine treatment an additional increase in mean walking distance, comparable to that seen during the first half of the study, was observed in these subjects. This improvement failed to reach a level of statistical significance because of the variation in response between individual patients.


Antihypertensive effect of oxprenolol and chlorthalidone in fixed combination, given once daily.

In a multicentre, single-blind, within-patient study, the effectiveness and tolerability of the fixed combination oxprenolol 80 mg + chlorthalidone 10 mg per tablet given once daily, compared to the well established b.i.d. schedule, has been investigated in forty out-patients with mild to moderate hypertension. After a two-weeks placebo wash-out, twenty patients were given 1 tablet b.i.d. of the fixed combination for 4 weeks and thereafter 2 tablets once-daily for a further 4 weeks; the remaining twenty patients were given the fixed combination in the reverse order. There was no significant difference in clinical response between the two treatment regimes, which were equally effective and well tolerated. However, patient compliance might be considerably improved with the once-daily dosage schedule of the fixed combination.


Oxymetazoline in the treatment of allergic and non-infectious conjunctivitis.

In a double-blind study of 141 patients, 0.025% oxymetazoline ophthalmic solution was compared with its vehicle in the treatment of allergic and non-infectious conjunctivitis. There was a marked difference in response at the first evaluation. By the tenth day (second evaluation) the total improvement in hyperaemia was 95% for oxymetazoline compared to 54% for the placebo. Oxymetazoline's decongestant effect in the eye matches its effect as a nasal vasoconstrictor.


A general practice trial of an amoxycillin/flucloxacillin combination (Suprapen) in proven bacterial infections.

Ninety-three cases of proven bacterial infection occurring in general practice were treated with an amoxycillin/flucloxacillin combination. There was a satisfactory clinical response in 98% of patients and an overall bacteriological success rate of 95.7%. Eleven patients (9.1%) complained of side-effects but withdrawal of the combination was necessary in only one patient who developed a rash.


Recurrence of otitis media after antibiotic therapy: comparison of cephradine and amoxycillin.

The long-term effectiveness of cephradine and amoxycillin in the treatment of otitis media was evaluated in one hundred children ranging in age from 4 months to 14 years. The immediate clinical response was comparable in both treatment groups, but the recurrence rate during a 12-month follow-up period was considerably lower in the patients treated with cephradine. The incidence of side-effects was similar in the two groups.


A single dose placebo-controlled study to assess the effectiveness of adding a muscle relaxant to a compound analgesic in the treatment of tension headache.

A patient-assessment of pain relief over 4 hours following a single dose of a compound analgesic has shown that 78% of patients achieve satisfactory relief of pain due to tension headache and that this response is enhanced by the addition of chlormezanone, an agent with reported anxiolytic and muscle relaxant actions. Side-effects were minor in nature.


Protective efficacy of live influenza vaccines. Its assessment in field and experimental conditions.

Cost benefit estimates of immunization programs are critically dependent on an accurate and reliable assessment of the protection offered by the vaccines. Consequently, the selection of appropriate parameters of protection becomes an issue of major importance. The protective efficacy of live influenza virus vaccines has been established for several vaccinal strains used in routine immunization. This was established under conditions of natural and artificial exposure to both homologous and heterologous influenza viruses. Reduction in the incidence of specific disease--respiratory illness, confirmed by influenza virus isolation and/or four-fold increase in serum HAI titer, was found to be significant. These data will be discussed in relation to available epidemiological models that have been developed for the evaluation of disease modifying properties of immunoprophylactic agents.


Problems in the investigation of adverse reactions.

All drugs and vaccines administered to man cause adverse reactions. In general the adverse reaction profile of a new vaccine should be defined in its clinical trial phase, but the incidence of adverse reactions occurring infrequently is likely to emerge only after extensive clinical use. Problems in the investigation and assessment of reports of adverse reactions which occur infrequently are reviewed. It is important that case reports be complete and include details of the batch number and manufacturer of the incriminated vaccine, and of its storage and administration. The assessment of reports of adverse reactions, which are similar in nature to those occurring in equivalent unvaccinated populations, presents special problems and may require case control studies. As new types of vaccines are developed it will be necessary to improve systems which monitor the occurrence of adverse reactions which occur infrequently and those which bear a distant time relationship to immunisation.


Effect of N-carboxymethyl-N-nitrosourea on viability and mutagenic response of repair-deficient strains of Escherichia coli.

Under simulated human gastric conditions, glycocyamine which exists in meat is known to be converted into N-carboxymethyl-N-nitrosourea (CMNU) by reaction with sodium nitrite. Because of its suspected hazards to man, CMNU was tested for its mutagenicity and lethal activity with a set of isogenic strains of Escherichia coli possessing the same auxotrophic marker but different DNA-repair capacities. Both strains NG30 (recA-) and R15 (polA-) were far more sensitive to lethality induced by CMNU than H/r30R (wild) and Hs30R (uvrA-) strains. The uvrA- strain was more sensitive to induction of mutations by CMNU than the wild and polA- strains, but the recA- strain was hardly mutable by CMNU. It can be concluded from these findings that the major cause of lethality of CMNU in E. coli is different from that of mutation induction.


[The influence of radium therapie on the yeast contamination of the vagina (author's transl)].

Before the beginning of radium therapy a vaginal yeast contamination of 9,7% was found of 113 patients with different genital carcinomas. However, the incidence of vaginal yeast contamination increased suddenly to 30,9% under the contac irradiation therapy with radium. The radiation effect of radium is not sufficient for a "selfsterilisation" of the radium-carrier in the case of yeast contamination. Therefore, a chemic desinfection of the radium-carriers is principly necessary. The significance of radium therapy with respect to vaginal yeast contamination is discussed and the recommendation is made that routine mycological supervision be carried out on all patients with gynaecological carcinomas and appropriate antimycotic therapy initiated where necessary.


Specificity of insertion by the translocatable tetracycline-resistance element Tn10.

Genetic analysis of 131 independent transpositions of the tetracycline-resistance element Tn10 from a single site in phage P22 into the histidine operon of Salmonella typhimurium reveals that Tn10 insertions are not randomly distributed along this chromosomal target. The insertions occur in 22 different "clusters"; insertions within each cluster are very tightly linked in recombination tests. Tn10 insertions are not evenly distributed among the identified clusters. The existence of these clusters suggests that this chromosomal target contains particular genetic signals that guide Tn10 to particular preferred positions for insertion. Insertions within each cluster occur in both orientations with roughly equal frequency.--The relationship among different insertions within each cluster has been examined. The resolution of genetic mapping places an upper limit of about 50 basepairs on the distance between different insertions within a cluster. Different insertions within a cluster usually have the same reversion frequency; however, heterogeneity in reversion frequency has been detected in at least two clusters. For most clusters, the available data are consistent with the simple possibility that all insertions within a cluster are at identical positions; however, the data do not exclude other possibilities.


Isolation and characterization of dnaX and dnaY temperature-sensitive mutants of Escherichia coli.

Escherichia coli mutants with temperature-sensitive (ts) mutations in dnaX and dnaY genes have been isolated. Based on transduction by phage P1, dnaX and Y have been mapped at minutes 10.4--10.5 and 12.1, respectively, in the sequence dnaX purE dnaY. Both dna Xts36 and Yts10 are recessive to wild-type alleles present on episomes. F13 carries both dnaX+ and Y+; the shorter F210 carries dnaY+, but not X+. Lambda tranducing phages that carry dnaX+ or Y+ have been isolated, and hybrid plasmids of Col E1 and E. coli DNA from the Clarke and Carbon (1976) collection also carry portions of the dnaX purE dnaY region. Results obtained with the lambda transducing phages and the hybrid plasmids suggest that dnaX is a different gene from the previously characterized dnaZ gene, which is also near minute 10.5--The dnaXts36 mutant, after a shift to 42 degrees, stopped DNA synthesis gradually, and the total amount of DNA increased two-fold. When this mutant was shifted to 44 degrees, the rate of DNA synthesis dropped immediately and the final increment of DNA was only 10% of the initial amount. Replicative DNA synthesis in toluene-treated cells was completely inhibited at 42 degrees and was partially inhibited even at 30 degrees.--When the dnaYts10 mutant was shifted to 42 degrees, DNA synthesis gradually stopped, and the amount of DNA increased 3.6-fold. At 44 degrees, residual DNA synthesis amounted to a two-fold increase. Replicative DNA synthesis in vitro in toluene-treated cells was inactivated after 20 minutes at 42 degrees or by "preincubation" of cells at 42 degrees before toluene treatment.--The dnaX and dnaY products probably function in polymerization of DNA, although participation also in initiation cannot be excluded.


[Asymmetry in the frequencies of reciprocal recombinants in crosses of T4 phage rIIB mutants].

The frequencies of reciprocal recombinants in crosses between rIIB mutants of T4 phage were shown to differ from each other. In terms of the correction model, this asymmetry of genetic recombination was used to measure the comparative correctability of the mismatched regions to the wild type and to the mutant alleles. The data obtained are in quantitative agreement with the analogous values for the same mismatched regions determined by comparison of the markers located at the same site. This strongly suggests that the asymmetry of genetic recombination in T4 reflects the corresponding difference in rates of correction of the mismatched regions in heteroduplexes in opposite directions.


[Incorporation of the ampicillin resistance transposon into the Escherichia coli K-12 chromosome and into plasmids].

The mutant pEG1 of R-factor RP4 with temperature-sensitive defect in replication, carrying a transposable ampicillin resistance element Tn1 was used to define the frequency of insertion of this element into Escherichia coli K-12 chromosome and some other plasmids. Our results indicate that the frequency of colony forming by bacteria with pEG1-factor on ampicillin medium in non-permissive conditions corresponds to the frequency of Tn1 insertion into bacterial chromosome or some other plasmid (in case when the strains are carrying a second plasmid). The frequency of Tn1 insertion into the chromosome is about 4.10(-4). The defect in recA gene produce no serious change in the frequency of Tn1 insertion into the bacterial chromosome. The translocation of Tn1 element from pEG1-factor to R483, R6 and ColE1 plasmids occurs at 10 to 100-fold-higher frequency than from the plasmid to the chromosome. The insertion of Tn1 into the F'-factor KLF10 and R-factor R64-11 occurs at far lower frequency than that to plasmids R6, R483, or ColE1.


[Plasmid transformation of frozen and thawed bacteria].

Plasmid DNA transformation efficiency depends on three essential factors: 1) the optimal regime of the recipients freezing-thawing; 2) the period of the recipients competence preservation; 3) individual sensitivity of microorganisms to freezing-thawing. It is demonstrated that plasmid DNA pMB9 activity indices are of maximal value during freezing at -70 degrees C or -196 degrees C and thawing at 42 degrees C. The short period of the competence, about 15 seconds, determines the rate of its infection. In this case it was achieved by mutual freezing-thawing of bacteria and DNA pMB9. The optimal yield of transformants is obtained in the following conditions: the concentration of bacteria - 1 - 5.10(9) cells/ml, the concentration of DNA pMB9 - 0.05--0.5 mcg/ml in the reaction mixture containing 0.5--1% of bactopeptone ("Spofa") and at pH 7.4--7.6.


Host dependence of RP1-specified resistance to ampicillin: differential expression in Escherichia coli and Rhizobium leguminosarum.

Rhizobium leguminosarum L4 is able to serve as a host for the plasmid RP1. Properties of R. leguminosarum [RP1] plasmid carrier suggest that the expression of RP1-coded Apr gene(s) is inhibited in this host, although the determinants of transfer and resistance to kanamycin and tetracycline are expressed. This system exemplifies a differential expression of plasmid genes in a new host.


Cephalic phase of gastric secretion in healthy subjects and duodenal ulcer patients: role of vagal innervation.

In 10 healthy subjects and 25 duodenal ulcer patients, gastric acid and pepsin and serum gastrin responses to cephalic-vagal stimulation induced by modified sham-feeding (MSF) were studied before and after vagotomy and atropinisation and compared with those to maximal stimulation with pentagastrin. When the MSF-induced peak acid output was normalised as a percentage of peak response to pentagastrin it was about 62% in healthy subjects and 66% in duodenal ulcer patients. Serum gastrin concentration was not changed significantly by modified sham-feeding either in normal subjects or in duodenal ulcer patients. Truncal vagotomy completely abolished gastric acid and pepsin responses to MSF in duodenal ulcer patients. Atropine almost completely suppressed gastric acid and pepsin responses to MSF in healthy subjects and reduced those in duodenal ulcer patients by about 62%. The combination of the modified sham-feeding and pentagastrin infusion resulted in augmentation of the acid output in duodenal ulcer patients but not in healthy subjects. This study shows that the cephalic phase results in a potent gastric acid and pepsin stimulation which is not accompanied by any change in serum gastrin concentration either in healthy subjects or duodenal ulcer patients and which is abolished by vagotomy and suppressed by atropine.


Controlled trial of cimetidine in upper gastrointestinal haemorrhage.

One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.


Collagen types and anticollagen-antibodies in Dupuytren's disease.

The relative proportion of collagen type I and type III in the aponeurosis of twenty-four patients with Dupuytren's disease was determined and compared with the aponeurosis of normal persons. The presence of considerable amounts of type III collagen was found in the Dupuytren's disease patients. The sera of the patients were screened for circulating anti-collagen antibodies using a sensitive radioimmunoassay. In seven out of the twenty-four patients low concentrations of these antibodies were found.


Free groin flap transfer to the upper extremity.

Seven patients underwent free groin flap transfer to the first web space, palm, wrist or elbow. Six of the seven were successful. The seventh developed acute venous occlusion and superficial necrosis of part of the flap, receiving split thickness skin grafts to salvage the dermal portion. Transfer is offered as an alternative to more conventional flaps for coverage of defects of the upper extremity.


The pattern of hand injury sustained in the overturning motor vehicle.

This is a review of six patients presenting with severe injuries of the dorsum of the hand following motor vehicle accidents. In each case the injury was sustained by the hand being trapped between the road and the overturning vehicle. The injured hands were either outside the window or passed through the open window at the time of the accident. These injuries were all sustained during the summer months.


[Health damage by means of forced smoking].

Forced smoking (= passive smoking) is not only a molestation but a real health risk for nonsmokers. The reasons for this are given in detail by a survey of results of the world literature. The main reasons are: In tobacco smoke are more than 40 cancerogenic substances which show a clear summative effect in contrast to other poisons. Avoidable cancerogens therefore must be eliminated from our environment wherever it is possible. There is no reason to make an exception with tobacco smoke. Special attention is to be paid to more than a dozen of cancerogenic nitrosamines in tobacco smoke. The content of nitrosamines in sidestream-smoke is up to fifty times higher than in the main stream of the tobacco smoke. Tobacco smoke therefore is the most important source of nitrosamines in our environment at all. The cancerogenic effect of passive smoking is secured in animal experiments unobjectionably. Passive smoking is the most important cause of bronchitis and pneumonia in early childhood and favours inflammations of the respiratory tract in older children and in animal experiments, etc.


[Bacterial vaginal fluor in intrauterine contraception].

Vaginal swabs obtained from 100 IUD-users were examined bacteriologically. Fifty-one women had vaginal discharge and 49 women used as control group had no complaints originating either from the IUD or from the genital tract. In the group of IUD-users with vaginal discharge the number of bacterial isolates was higher and the cultures were more diversified. The nulliparous patients in this group exhibited more anaerobic cultures than the IUD-users without discharge. The significance of vaginal discharge in IUD-users is its function as a pool for pathogenic bacteria which may provoke and/or maintain inflammatory diseases of the female genital tract. IUD-users with vaginal discharge do therefore need not only bacteriologic diagnosis, but also consequent treatment of the discharge.


[Experiences in the use of Essaven capsules in the treatment of venous leg diseases. Results of a double-blind study].

The efficacy of Essaven-capsules in venous circulatory disorders of the leg was assessed under the conditions of everyday general practice in a double blind trial including 34 out-patients. During the 4 week-treatment Essaven proved to be significantly superior to a placebo of identical appearance as regards the parameter pain in the legs, skin lesions, circumference of the ankle, and diuretic performance. The dosage was 3 X 2 capsules per day.


[A simple method for the transfer of tomography scan layers to the X-ray film, especially in functional neurosurgery (author's transl)].

The article describes a new method enabling the transfer of CT scan layers to the X-ray film with simple means.


Clinical relevance of experimentally obtained electrophysiologic data on antiarrhythmic drugs.

An extrapolation of electrophysiological findings to a specific clinical situation is not always feasible since successful arrhythmia analysis frequently is not achieved and even in the presence of a known arrhythmic mechanism, the predominant effect of a given antiarrhythmic agent cannot be predicted with respect to therapeutic relevance. These assertions are additionally supported by the fact that the effects of antiarrhythmic agents, which have been primarily studied in healthy myocardium, may be entirely different in the presence of myocardial ischemia. Furthermore, in spite of a certain degree of agreement among data of experimentally-induced and clinical myocardial ischemia, the findings do not imply complete applicability. Theoretical considerations indicate that a reentry mechanism may not only be favourable influenced by an agent rendering improved conduction velocity and shortened refractory periods but also influenced by an agent effecting oppositely directed changes. Although an effective therapeutic regimen can generally be achieved with no exact knowledge of the arrhythmic mechanism or of the specific action of a given drug, future investigations hould augment existing information to yield a more rational means of treatment and prevention of arrhythmias as well as to aid in the development of new antiarrhythmic agents.


[Aortopulmonary window: external occlusion in the newborn (author's transl)].

Correction of aortopulmonary window in the newborn infant carries a high operative risk. Even later in life operative mortality with or without cardiopulmonary bypass may amount to 30% and more. To reduce the operative risk a new technique for closure of the aortopulmonary window was employed in 2 infants aged 3 and 4 weeks, respectively. With this method the communication is externally occluded by 4 or 5 mattress-sutures, buttressed with Dacron strips on each side. Both infants underwent emergency operation because of intractable heart failure. The postoperative course was uneventful and both were discharged from the hospital in good condition.


Use of catecholamines in acute myocardial infarction.

We review the hemodynamic effects and clinical usefulness of five natural and synthetic catecholamines. Their actions are best understood by an appreciation of the relative ability of each catecholamine to activate alpha, beta 1 and beta 2 adrenergic receptors in the myocardium and peripheral vasculature. Epinephrine, the first catecholamine isolated, is shown to have little useful role in the therapy of acute myocardial infarction. L-norepinephrine has powerful alpha and moderate beta 1 effects. It is the catecholamine of choice in the initial treatment of cardiogenic shock associated with acute myocardial infarction. Isproterenol markedly increases myocardial contractility and heart rate by beta 1 stimulation, while simultaneously decreasing peripheral vascular resistance and, therefore, arterial pressure through its action on beta 2 receptors. It increases cardiac output, but its metabolic costs are high in the presence of ischemia. Its role in the therapy of acute myocardial infarction has largely been supplanted by more selective agents. Dopamine causes slightly less vasoconstriction than l-norepinephrine and slightly less myocardial stimulation than isoproterenol. In low doses, it increases renal and mesenteric blood flow by activation of a non-adrenergic receptor. Tachycardia and associated metabolic deterioration render it a second-line drug in the treatment of severe cardiogenic shock. Dobutamine, a new synthetic catecholamine, has primarily beta 1 activity. It increases myocardial contractility with little effect on heart rate or peripheral vascular resistance. It is ineffective in cardiogenic shock, but may eventually be shown to have a role in the treatment of left ventricular failure uncomplicated by severe hypotension.


[Platelet suppressant therapy and oral anticoagulants in the secondary prevention of acute myocardial infarction (authors transl)].

First positive results with platelet suppressant drugs in the secondary prevention of acute myocardial infarction have engendered optimism in the medical and lay community alike. A review of the subject therefore seems appropriate. In the same context a critical reappraisal of the value of long-term anticoagulant therapy after acute myocardial infarction appears also warranted. Results with platelet suppressant therapy reported so far are favorable; however, they fall short from establishing definite proof of the value of such therapy after myocardial infarction. Accordingly, limited clinical use of platelet suppressants may be justifiable by now; it should be borne in mind, however, that such use at the present time still has to be considered experimental. In contrast, there has been statistically well-founded evidence that long-term anticoagulant therapy lowers the mortality after myocardial infarction. It is true, however, that the profit is rather small and that it can be achieved only under rigid control of anticoagulant therapy. Therefore the pros and the cons have to be weighed very carefully for every individual patient, before long-term therapy with oral anticoagulants is started after an acute myocardial infarction. Several large clinical studies are close to completion. It is to be hoped that their outcome will decide, whether platelet suppressant drugs will entirely replace oral anticoagulants in the secondary prevention of acute myocardial infarction.


[Respiratory distress in the newborn (author's transl)].

Diseases which manifest with the respiratory distress in the newborn include 1) respiratory diseases-IRDS, type II RDS, neonatal asphyxia, and MAS etc. 2) anemia, CHD 3) CNS and 4) metabolic diseases. Among these, IRDS has high mortality rate because of the lack of the pulmonary surfactant and immaturity of respiratory center, and has many difficult problems in terms of its prevention and respiratory management. The points of its respiratory management are as follows: 1) Estimation of the level of arterial oxygen ation-this is the most important point. It has become possible, these days, to monitor continuous oxygenation using a transcutaneous oxygen electrode. 2) Knowledge of the physiology & management of apnea, and monitoring of heart rate and respiration. 3) Correction of acidosis & anemia and the nutritional supply by the intraveonous fluid administration. 4) Airway maintenance. 5) Oxygen administration to main PaO2 or tc PO2 of 60--80 mmHg. 6) Artificial ventilation by CPAP or IMV and 7) The specific drug therapy includes indomethacin for PDA associated with IRDS, Tolazoline for the fetal circulation syndrome, and Xanthine derivatives for primary apnea. 8) However, improvement by exchange transfusion has been contro-versial. On the other hand, in the type II RDS which has a relatively good prognosis, the intact survival can be expected by means of the proper management of general condition and respiration. In MAS, pneumothorax, pneumomediastinum and severe asphyxia, the proper resuscitation, oxygen administration should be given according to several conditions, especially the degree of hypoxia. The peritoneal dialysis can be lifesaving in case of severe renal impairment with RD. As the respiratory distress in the newborn is very frequent in its occurrence and death rate, its proper management is expected to result in the decrease in the newborn death rate in Hokkaido (8.1--6.6 per 1,000 live births) and the increase in the survival rate without any handicap, particularly if hospitals in each Hokkaido district give the newborn medical care more intensively than at present.


Direct effect of corticosterone upon insulin secretion studied by three different techniques.

The immediate effect of corticosterone upon insulin secretion rates estimated by three different techniques (perfusior of isolated rat pancreas and perifusion or incubation of isolated islets of Langerhans) was studied for one hour. Three corticosterone concentrations were used: 0.02, 0.2 or 20 mg/l. With 4.2 mmol/l glucose, corticosterone did not affect insulin secretion, whereas, with a stimulating glucose concentration (16.7 mmol/l), insulin secretion was inhibited by the three corticosterone concentrations tested during incubation experiments, and by only the two physiological ones (0.02 and 0.2 mg/l) during islets perifusion and pancreas perfusion experiments. Moreover the inhibitory effect appeared more rapid with perifused islets than perfused pancreas, where only the second insulin secretory phase was disturbed.


Elucidation of an A and L system for amino acid transport in the human lymphoblast using a membrane filtration technique.

Optimum conditions have been established for the measurement of amino acid transport by human lymphoblastoid cell lines using a membrane-filtration technique. The parameters we found to be important for the reproducibility of the method are: the types and combination of filters, the strength of the vacuum applied to the filters and the density of the cultures at the time of harvesting and during uptake and filtration. We found that bovine serum albumin added to phosphate buffered saline (PBS) glucose in which the cells are washed, resuspended and assayed is essential for the maintenance of viability, the prevention of clumping and the retention of the accumulated amino acid. Using this procedure we have characterized two transport systems for the neutral amino acids; an A and an L system, which are similar but not identical to the A and L systems characterized in rodent cell lines. These A and L systems have characteristically lower Km's and Vm's for alanine and phenylalanine, when compared to rodent cell lines. In addition, we find alpha-AIB to be a poor competitor of alanine and phenylalanine uptake.


The location of tick salivary antigens, complement and immunoglobulin in the skin of guinea-pigs infested with Dermacentor andersoni larvae.

Using indirect immunoflorescence techniques, tick salivary gland antigens (SGA) were demonstrable in cement deposited on the skin by ticks and in all layers of the epidermis of infested guinea-pigs close to the sites where ticks attached. The antigen remained in these sites for several days after ticks had detached. In tick-resistant but not in normal guinea-pigs, SGA, complement and IgG were deposited at the dermo-epidermal junction even at some distance from the attachment site. Complement was also demonstrable in epidermal vesicles which developed beneath larvae attached to resistant guinea-pigs. It is suggested that antigen-antibody reaction and complement activation at these sites may play a role in the development of skin lesions and the attraction of basophils to these areas in challenged tick-resistant guinea-pigs. Tick antigens were also found to be associated with dendritic suprabasal cells in the epidermis of resistant guinea-pigs. It has previously been proposed that such SGA-trapping cells are Langerhans cells. These cells, in the presence of specific antibody and complement, could also initiate epidermal lesions in resistant guinea-pigs.


In situ formation of antigen-antibody complexes in the mouse glomerulus.

Intravenous administration of heat-aggregated bovine serum albumin (BSA) to mice resulted in localization of micro-particulate BSA in the mesangial region of the glomerulus. Subsequent intravenous administration of rabbit anti-BSA antibody at a time when no free antigen remained in the circulation produced localization of antibody and fixation of mouse complement within the glomerulus in a pattern corresponding to that of the heat-aggregated BSA. This apparent in situ formation of immune complexes in the glomerulus is similar to that of the classical Arthus phenomenon in the skin.


Suppressed or enhanced antibody responses in vitro after BCG treatment of mice: importance of BCG viability.

Mycobacterium bovis, BCG, is known to be capable of either enhancing or suppressing various immune responses. Using a standard technique and number of organisms, some of the parameters predetermining whether enhancement or supression will occur have been investigated. Dead BCG given intravenously into mice caused an enhancement of the antibody response in vitro to sheep erythrocytes. In contrast, the same number of viable organisms caused suppression if given intravenously but enhancement if given subcutaneously. The inclusion of 25% or more killed organisms in an intravenous inoculum of fully viable organisms changed suppression to enhancement. Treatment of BCG infected mice with streptomycin lessened the suppression but did not change it to enhancement. The possible causes of suppression are discussed.


The immune response of mice to bacterial antigens given by mouth.

The secretory and systemic antibody responses to oral dead Escherichia coli were examined in A strain mice. The best responses were obtained in mice dosed with 1 x 10(10) bacteria. Orally immunized animals showed an enhanced response to subsequent parenteral immunization with somatic antigens. This effect could be passively transferred with serum. In contrast, the response to the capsular antigen K88 was reduced in the same animals.


The binding of LPS to the lymphocyte surface.

Bacterial lipopolysaccharide (LPS) from Escherichia coli labelled with tritium has been used to follow the binding of LPS to lymphocytes. Binding to cells rose to a maximum 2-7 min after addition of [3H]-LPS, followed by loss of [3H]-LPS from cells, reducing to about 10% of the peak level at 20-30 min. Peripheral blood lymphocytes, mesenteric lymph node and thymus cells of the pig and CBA, C3H/He and C3H/HeJ mouse spleen cells all bound [3H]-LPS transiently at similar levels. It is concluded that this type of LPS binding cannot be solely responsible for the preferential stimulation of B cells by LPS.


Specific suppression of delayed hypersensitivity response to sheep erythrocytes by heterologous anti-lymphocyte serum.

The development of a heterologous anti-lymphocyte serum (ALS) capable of specifically suppressing the delayed hypersensitivity (DH) response is reported. This ALS, termed ALS(CMI), was prepared against lymph node cells from rats which had been immunized against sheep erythrocytes (SRBC) following treatment with cyclophosphamide which is known to enhance the DH response and suppress the humoral immune response. The effect of ALS(CMI) on the primary DH response to SRBC using the footpad swelling test was studied. Its effect on the primary humoral immune response to SRBC was also studied using the Jerne plaque assay technique. ALS(CMI) suppressed the humoral antibody response to SRBC and the DH response to a third party antigen only when administered before the antigen, having no effect when administered post-antigenically. On the other hand, ALS(CMI) significantly suppressed the primary DH response to SRBC when administered either before or after the antigen.


Anti-DNP antibody responses to DNP-histone H1 in mice.

Anti-DNP antibody responses to DNP-histone H1 in C3H/HeN mice were not suppressed by in vivo treatment with carrageenan in which many phagocytic macrophages were presumed to be impaired. Rather higher antibody responses to this antigen were observed in athymic nude mice than in heterozygous nude mice. Further, non-adherent spleen-cell and T-cell depleted spleen cells induced in vitro anti-DNP antibody responses to DNP-histone H1 to the same extent as normal spleen cells. These results suggest that anti-DNP antibody responses to DNP-histone H1 are macrophage- and thymus-independent. It was also observed that IgG-type anti-DNP antibodies to DNP-histone H1 were produced although most thymus-independent antigens were shown to induce predominantly IgM type antibodies but little, if any, IgG type antibodies. Furthermore, histone H1 did not show any polyclonal B-cell activator activities in contrast to many other thymus-independent antigens which act as polyclonal B-cell activators.


Acinetobacter and E. coli lipopolysaccharide preparations comparative mitogenicity and induction in vitro of immunoglobulin synthesis in adult and neonatal pig lymphocytes.

Lipopolysaccharide (LPS) was prepared by phenol/water extraction of bacterial membranes prepared from Acinetobacter and Escherichia coli. The mitogenicity of laboratory-prepared LPS was significantly greater than that of commercial E. coli LPS for pig, sheep, calf and rat lymphocytes, assayed as [3H]-thymidine incorporation. Mouse lymphocytes responded well to commercial LPS and no greater response was obtained with other LPS preparations. A small proportion (14%) of the Acinetobacter LPS preparations was soluble in aqueous medium, the remainder comprising membraneous fragments of variable form and size. It is suggested that the insoluble presentation of LPS to cells may contribute to the improved mitogenicity compared with wholly soluble LPS. Acinetobacter LPS preparations were used to induce synthesis and secretion in vitro of immunoglobulin by adult blood lymphocytes and pre-suckled, neonatal spleen cells of the pig. IgM was the dominant class of immunoglobulin secreted. This work thus demonstrated that virgin, unprimed B cells could be induced into immunoglobulin secretion by mitogen stimulation.


MHC restriction of murine T lymphocyte reactivity analysed by growth of bone marrow cells in vitro on thymus epithelial monolayers.

Mature mouse T lymphocytes, derived from long-term culture of bone marrow cells on thymus epithelial monolayers, were analysed with respect to their ability to co-operate with B cells (for antibody production) or T cells (in the generation of cytotoxic cells) when the bone marrow T precursor cells and the thymus epithelial cells differ at defined regions of the major histocompatibility complex. A pool of more mature bone marrow T-cell precursors gave rise to T cells interacting only with T/B lymphocytes sharing MHC determinants with the strain of origin of the bone marrow cells used. In contrast, a more immature bone marrow T-cell precursor pool produced T lymphocytes which had acquired MHC restriction (in terms of co-operativity with T/B cells) as defined by the MHC determinants of the thymus epithelium, and not those MHC determinants of the cultured bone marrow population. In addition, some evidence was obtained for Ir gene control (mapping in the MHC region) in the development of the repertoire of T cells involved in production of cytotoxic responses in vitro to TNP-modified self antigens.


Central vein thrombosis: a complication of internal jugular vein cannulation.

Clinical signs of central vein thrombosis as a complication of internal jugular vein cannulation are rarely seen. Two infants who developed thrombosis of the superior vena cava and one adult who developed thrombosis of the left brachiocephalic vein are presented.


["Old new" problem of the lues risk in transfusion medicine: the effect of the serum and ACD stabilizer at different temperatures on the infectiosity of Treponema pallidium (Nichols strain)].

The portion of warm and fresh blood transfusions had increased obviously. This is accompanied by a decrease of the restrictive period of the former 72 and the presently 48 hours for blood units to be transfused. Therefore, the danger of a symphilis transmitted by transfusion is impending again. This is realized insufficiently and the syphilis may occur, if blood is drawn in the seronegative phase of the primary stage of syphilis and transfused within the restrictive period. Model trials on the infectivity of Treponema pallidum revealed that the syphilis cannot be transmitted by blood and its derivates drawn in the seronegative phase after storage at 4 degrees C for 24 hours. Therefore, the reduction of the restrictive period to 48 hours is justified.


Kidney donation--where some of the problems lie.

If a viable kidney transplant programme is to be continued on a national basis, many of the problems at present surrounding organ transplantation must be tackled urgently. This paper discusses the psychological and emotional problems which are presently seen to hinder a successful renal transplantation policy, and considers the relative advantages and disadvantages of the kidney donor card scheme.


Open fractures of the shaft of the tibia: analysis of wound and fracture treatment.

Cooperation between orthopaedic and plastic surgeons is an important factor in the treatment of open fractures. In this article a report is made on a retrospective study of a 5-year series of open fractures of the shaft of the tibia treated at the University Hospital in Uppsala between 1972 and 1976. The study proves that the change to external fixation of these fractures and 'open' treatment of the wounds has meant that to a large extent the previous use of pedicle flaps to cover skin defects has been replaced by split skin grafts. The results in the reported series were good, with adequate function in most cases. The final results may, however, be less good than they appeared at this early review time.


Etiology and pathophysiology of malignant hyperthermia.

MH occurs in people who have a generalized membrane abnormality. Two clinical myopathies are known to be associated with this membrane defect. One is usually subclinical and is inherited as a mendelian dominant characteristic. The other occurs in boys who have a number of striking physical abnormalities, and is inherited as a recessive trait. When the abnormal muscle cell membrane is exposed to anesthetic agents such as halothane or succinylcholine there is a rapid, excessive release of calcium into the myoplasm. The raised myoplasmic calcium concentration leads to all the clinical features of the syndrome, predominant among which are: metabolic acidosis, a rise in body temperature, and rigidity--particularly in the muscles of the limbs. The exact site and nature of the lesion in the muscle cell membrane are still to be determined, but recent evidence suggests that it may lie in the E-C coupling mechanism. Understanding of the pathophysiology of MH has led to the development of an appropriate drug treatment for this syndrome, the aim of which is to restore the elevated myoplasmic calcium level to normal. Dantrolene sodium promises to be the most effective drug in achieving this result.


Minimal side-chain protection can be a successful strategy in solid-phase peptide synthesis.

The N-terminal tyrosine residue of Met-enkephalin could be readily incorporated without protection of its phenolic hydroxylgroup. Furthermore, the HF-cleaved product contained fewer impurities than that derived from hydroxyl-protected material. Despite the presence of Tyr in the center of the chain, an LH-RH antagonist, [D-Phe2, D-Trp3, D-Phe6]-LH-RH, could also be made in normal yield by incorporation of free Boc-Tyr. Syntheses of the same model peptide without protection of the Ser residue and protection of the Arg residue as the guanidine HCl salt also gave excellent yields of analog. Finally, the LH-RH inhibitor and a highly active agonist, [D-Leu6, desGly-NH2(10)]-LH-RH ethylamide, were synthesized without protection of Tyr, Ser and Arg, which enabled free peptides to be generated directly by ammonolysis and ethylaminolysis, respectively, without HF treatment. In all examples, no evidence emerged to suggest reaction of side-chains during synthesis.


The problems of generations: and generational analysis.

The focus of this paper is two fold: 1. conceptual and methodological problems underlying the life-span sociology literature that heretofore have not been discussed; and 2. application of the generational analysis model to the question of life cycle change in personal values. Specifically, we address the issues of whether (1) value change over the life course is a result of period shifts or individual maturation and (2) differences in values among age strata are a function of cohort experience or individual maturation (aging). Utilizing data from the Detroit Area Studies, four measures of values were constructed. The analyses shows that on only one of the four dependent measures was aging directly implicated in the findings. However, cohort differences and period effects were found to have a significant effect on the distribution of several of the value indices. The data are consistent with Mannheim's observation that older cohorts are affected by social change although the relative degree of observed change is much greater among the young.


Charles Dickens' old people.

Charles Dickens, rare among authors of any period, presented a host of elderly and old characters in his novels and stories. More than 120 such characters were identified, distributed among four levels of involvement (protagonist to minor role) and six categories of behavior (warm and sympathetic to villainous and threatening). The two-thirds male, one-third female characters tended to be concentrated at the minor, rather than major, levels of involvement in plots, but they represented a great range of behavior. Dickens' old people were fully engaged in life and society and were not age-stereotyped.


Retinal detachments and intraocular lenses.

1. Increasingly more patients with PPRD are seen. A retinal detachment can occur after any type of implant or cataract extraction. 2. The pseudophakic patient is better equipped than the aphakic patient to recognize symptoms of a retinal detachment, and most PPRDs are seen soon after they occur. 3. Visual access to the retina is sometimes decreased. The IOL requires more precautions. Hazy media and lens remnants are a major handicap, and the examination is more difficult and time-consuming. 4. Characteristic pseudophakogenic retinal changes or breaks are not obvious. Retinal tears are small and located near the ora serrata retinae. 5. When the breaks are found, the lengthy examination can be followed by a simple scleral buckle with minimal insult to the eye. When the breaks are not found, the treatment is extensive. 6. The anatomical and visual results are comparable to results of other rhegmatogeneous retinal detachments.


The clinical and psychological effects of pemoline in depressed patients--a controlled study.

The clinical and psychological effects of pemoline were compared with placebo in a double-blind study of 20 depressed patients. Target symptoms were disturbances of concentration and memory, tension, depression, fatigue, decreased libido, anorexia and insomnia. The two groups were matched for their clinical picture, age, sex, and duration of illness. During the three-week study period the pemoline group received 50 mg daily. Significant differences in some clinical symptoms were found between the groups, but not in the performance of psychological tests, administered before and after the three-week study period. These differences proved the effectiveness of pemoline in combating symptoms of disturbances in concentration, memory, tension, depression and fatigue.


[Treatment of lithium tremor with the beta receptor blocker, pindolol].

In a cross-over study with Pindolol, 15 mg/day, against placebo, we studied during 4 weeks 22 patients aged between 20 and 65 years who where treated by means of lithium carbonate retard (Quilonum Retard). The tremor was measured twice a week by means of three apparative methods: an accelerometer, a 'hole-plate' and an 'aimed tapping plate', both constructed by Janke, and was also studied by means of a self-evaluation rating-scale. We obtained a positive therapeutic effect of Pindolol on lithium-induced tremor, which was statistically significant by means of the 'hole-plate' and of self-evaluation. Differences in results are discussed.


[Importance of the plasma membrane for epidermal regulation processes].

In this review the general structure and the properties of the plasma membrane are described with respect to the recent findings on the membrane of the keratinocyte. A structural and functional model of the plasma membrane of the keratinocyte is proposed based on biochemical, electron microscopic and fluorescence microscopic findings. The plasma membrane is obviously involved in the control of intercellular adhesion, growth and differentiation of normal epidermal cells. Under pathological conditions an alteration of the plasma membrane of the keratinocyte may affect the intercellular communication and/or the cellular control by mediators.


Investment decision making in the health care industry: the future.

The economic and political environment in which providers of health care will operate during the 1980s will continue to be increasingly restrictive. Any private-sector organization's long-run survival depends directly on the quality of its investment decisions, broadly defined. This decision making will require three major innovations if private sector health care providers are to survive: 1) traditional biases about the economics of not-for-profit entities must be abandoned; 2) standard data, procedures, and personnel from the accounting discipline must be supplemented with information, methodologies, and people from the discipline of corporate finance; and 3) economic and fiscal risk must be measured and incorporated into both investment decisions and interactions with external regulators. Practitioners can begin to implement these innovations immediately. Although substantial literature exists developing all these concepts generally and applying them to for-profit settings, the literature purporting to treat investment decision making for private-sector health care providers is, on average, replete with conceptual error, simplistic thinking, erroneous applications, and out-of-date methodologies. The literature is, in a word, horrid. Authors, both practitioner and academic, should stop writing terrible books and booklike periodicals for easy royalty dollars, and, instead, pursue sound applied research and disseminate their results in classrooms and in refereed journals.


Transportation or CT scanners: a theory and method of health resources allocation.

Cost containment and access to appropriate care are the two most frequently discussed issues in contemporary health policy. Conceiving of the health services available in specific regions as "packages" of diverse items, the authors of this article consider the economic trade-offs among the various resources needed for appropriate care. In the discussion that follows, we examine the trade-offs between two divergent offering of the health care system: high technology medicine and support services. Specifically, we examine several strategies designed to achieve an optimal mix of investments in CT scanners and transportation resources in the South Chicago region. Using linear programming as a method for examining these options, the authors found that 1) the proper location of CT scanners is as important for cost containment as optimal number, and 2) excess capacity in the utilization of a single resource--CT scanners--need not imply inefficiency in the overall delivery of the service. These findings help demonstrate the importance of viewing health care as a package of interrelated services, both for achieving cost containment and for providing access to appropriate care.


Successful indomethacin treatment of two paediatric patients with severe tubulopathies. A boy with an unusual hypercalciuria and a girl with cystinosis.

Two children were followed for severe congenital tubulopathies: a boy presented an excessive sodium, calcium and water excretion; a girl had cystinosis and a De Toni-Debré-Fanconi syndrome. These renal defects were both associated with increased levels of plasma renin activity and aldosterone, and excessive urinary PGE1 production. They had been unresponsive to therapeutic attempts. Only indomethacin treatment was successful in reversing the biochemical abnormalities and improving the growth pattern.


Fluorescent colloidal gold: a cytochemical marker for fluorescent and electron microscopy.

The gold method was further developed for fluorescent microscopy. Gold granules (12 nm in size) were labelled with rhodamine conjugates of Concanavalin A and avidin. The fluorescent markers were used to mark cell wall mannan on the yeast Saccharomyces cerevisiae either by the one-step, or by the two-step method via a biotinyl derivative of ConA. By fluorescence or transmission electron microscopy, the two-step method was found to achieve a higher density of marking.


The avian proventriculus is an abundant source of endocrine cells with bombesin-like immunoreactivity.

Radioimmunoassays using specific bombesin antisera revealed high concentrations of immunoreactivity in the turkey proventriculus, and negligible amounts of activity elsewhere in the gut. In immunohistochemical studies the same antisera revealed abundant endocrine-like cells in proventriculus mucosa, and isolated cells in small intestinal mucosa. In contrast to the rat, immunoreactivity was not demonstrated in nerves.


Metastatic potential of malignant tumours.

The term 'metastatic potential' is examined, together with some of the factors that may contribute to it. The evidence is drawn from clinical and experimental sources. Morphological factors include the site of the tumour, its size, histological appearances and pattern of local spread. The scope and limitations of each are discussed and the potential application of newer morphological techniques is noted. Certain non-morphological factors are considered: these are (1) the functional heterogeneity of tumour cell populations with resepct to the metastatic capacity; (2) the elaboration of certain tumour-associated products which may potentiate tumour spread; and (3) immunological factors in the form of local host cell infiltrates in and around primary tumours. The tumour-associated products include collagenases, prostaglandins and angiogenesis factor; their likely origin from tumour and host cells is stressed, together with their implications in physiological and pathological processes other than neoplasia. It is concluded that the metastatic potential of tumours cannot be assessed in the terms of conventional tumour pathology alone. A more functional approach is needed before the term 'metastatic potential' acquires solid conceptual or practical value.


A review of histiocytosis X with particular reference to eosinophilic granuloma of the lung.

Electron microscopy confirms the unity of Histiocytosis X (HX) by identifying a common marker organelle in all three forms of the disease (acute disseminated HX or Letterer-Siwe disease; chronic disseminated HX or Hand-Schuller-Christian disease; localized HX or eosinophilic granuloma). The marker organelle of HX is also found in normal Langerhans' cells: these mononuclear cells are distinct from macrophages but are similarly concerned in antigen transport. HX may therefore be considered to represent a pathological proliferation of Langerhans' cells. The natural history and the clinical, radiological and pathological features of primary pulmonary HX (eosinophilic granuloma of the lungs) are described, together with the differential diagnoses which must be considered by the histopathologist.


[The emperor Nero as an example of the actor and singer in ancient Rome (author's transl)].

The question of what importance the human voice had as a means of expression in the Roman Empire and how orators, actors and singers trained and developed their voices can be seen in the example of the Emperor Nero (37--68 AD). The historians of late antiquity (in particular, Sueton and Tacitus) reported a deeper insight into Nero's complex personality. As a result, a number of details are known about his training as an artist as these relate to his appearance in public as an actor and singer. These findings can also be regarded as characteristic for the epoch of the time.


Cancer cachexia in man: a review.

There are many factors which are responsible for the high incidence of cachexia in human neoplasia. In this review, those considered to be of major importance are discussed. Nutritional disturbances, such as anorexia and malabsorption, are common and nutritional repletion may be beneficial to certain patients. Raised metabolic rate and energy expenditure are also encountered. Tumour cells may act as a nitrogen trap or energy sink, but the significance of these mechanisms in man is questionable. Ectopic hormone production by tumours is well established and a number of tumour-derived substances have been described which interfere with the intermediary metabolism of the host. The significance of these various substances also remains uncertain. Most experimental studies of cancer cachexia have utilized transplantable animal tumour models which bear a poor resemblance to the clinical condition. Development of more suitable models with human tumour xenografts might allow a quicker and better understanding of the aetiologies of human cancer-induced cachexia.


Pregnancy proteins: a review.

Pregnancy proteins can be conveniently divided into three groups, the so-called trophoblast-specific, the pregnancy-associated and the foetal proteins. In this review we have attempted to outline the physicochemical properties and clinical value of the pregnancy-specific and pregnancy-associated proteins in the monitoring of feto-placental function and malignant disease. Where possible, we have tried to indicate areas of future development.


Resistance plasmids in Pseudomonas cepacia 4G9.

Pseudomonas cepacia 4G9 utilizes 2-tridecanone as its sole carbon source and has been shown to be resistant to a variety of antibiotics. To ascertain whether any of these characteristics were plasmid mediated, Escherichia coli HB101 was transformed with plasmid DNA isolated from Pseudomonas cepacia 4G9. No 2-tridecanone-utilizing transformants were obtained. Tetracycline (Tc)- and ampicillin (Ap)- resistant transformants were obtained at a low frequency. Plasmid deoxyribonucleic acid from antibiotic-resistant E. coli HB101 transformants had molecular weights of 2.9 x 10(6) for pJW2 Tcr and 5.4 x 10(6) for pJW3 Apr as determined by electron microscopy. Electron microscopy of plasmid deoxyribonucleic acid from P. cepacia 4G9 revealed a single plasmid species, pJW1 of 1.78 x 10(6). Tetracycline resistance in both P. cepacia 4G9 and E. coli HB101(pJW2) was inducible, whereas ampicillin resistance in P. cepacia 4G9 was constitutive. The level of ampicillin resistance coded by pJW3 was lower in P. cepacia 4G9 than in the transformant E. coli HB101(pJW3).


Ploidy determination of Canadida albicans.

The dimorphic yeast Candida albicans, as a member of the fungi imperfecti, has been assumed to be in the haploid, or imperfect, state. The deoxyribonucleic acid content of this species has been measured by flow microfluorometry, a technique capable of analyzing single cells. These results were compared with flow microfluorometric deoxyribonucleic acid determinations on a series of strains of Saccharomyces cerevisiae of known ploidy (haploid, diploid, triploid, and tetraploid). These ploidy levels were readily distinguished by the flow microfluorometry procedure. By this criterion, C. albicans was found to contain a diploid amount of deoxyribonucleic acid. Ultraviolet radiation survival and chemical mutagenesis experiments support the conclusion that both clinically isolated and laboratory strains of C. albicans are diploid.


Interaction of bacteriophage T4 with reconstituted cell envelopes of Escherichia coli K-12.

The interaction with bacteriophage T4 of the cell surface of Escherichia coli K-12 reconstituted from outer membrane protein O-8, lipopolysaccharide, and the lipoprotein-bearing peptidoglycan sacculus was studied. The reconstituted cell surface was active as a receptor for the phage, resulting in the contraction of the tail sheath, a morphological change in the base plate which was accompanied by the extension of short tail pins down to the cell surface and the penetration of the needle through the cell surface. However, the ejection of phage deoxyribonucleic acid did not take place. Both O-8 and lipopolysaccharide were essential for the interaction. In the reconstitution, the wild-type lipopolysaccharide could not be replaced by either heptoseless lipopolysaccharide or lipid A. The lipoprotein-bearing peptidoglycan sacculus was also found to be an active component for the phage adsorption. The sacculus most likely functioned as a basal framework on which O-8 and lipopolysaccharide assembled to form a flat sheet which is large enough to interact with individual distal ends of long tail fibers of a single phage particle.


Hyaluronic acid capsule: strategy for oxygen resistance in group A streptococci.

Unencapsulated variants of encapsulated, M-protein-positive group A streptococci are oxygen sensitive and secrete inhibitory concentrations of hydrogen peroxide when grown in aerated broth cultures. The organisms were equally sensitive to hydrogen peroxide, and neither exhibited catalase or peroxidase activity, suggesting that differences in oxygen sensitivity reflect dissimilarity in oxygen uptake. The encapsulated parental culture was found to grow in aggregates that take up oxygen more slowly than unencapsulated, oxygen-sensitive derivatives. Moreover, the latter grow in an unaggregated, homogenous suspension. The enzyme hyaluronidase was able to disrupt aggregates of the encapsulated strain increase the rate that these cells take up oxygen, and cause the accumulation of toxic concentrations of hydrogen peroxide earlier in their growth cycle. The evidence presented shows that the aggregation of streptococcal cells by their hyaluronic acid capsule provides this organism with a novel means to avoid self-destruction by oxygen metabolites--cells are shielded from oxygen. The reduced surface-to-volume ratio and limited diffusion of oxygen into the interior of aggregates are proposed as the protective mechanism.


Existence of the bound form of prolipoprotein in Escherichia coli B cells treated with globomycin.

A murein-bound form of prolipoprotein was found in the cell envelope fraction of globomycin-treated Escherichia coli B. We suggest therefore that proteolytic cleavage of prolipoprotein to mature lipoprotein is not essential for the transpeptidation of the lipoprotein to peptidoglycan.


Direction of deoxyribonucleic acid transfer and replication in a derivative of plasmid R100-1.

The site of integration and the molecular orientation of a prophage Mu integrated within the resistance transfer factor component of plasmid R100-1 have been determined on the physical map of the plasmid. This allowed us (i) to determine the direction of deoxyribonucleic acid transfer from oriT during conjugation and (ii) to demonstrate the unidirectionality of replication in conditions of exponential growth (by determining the strand preference of Mu-specific Okazaki fragments).