Showing papers by "Uppsala University published in 1984"

Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients

Abstract: The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.

The distribution of hypoglycemic brain damage.

Abstract: Rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. After recovery with glucose, they were allowed to wake up and survive for 1 week. Control rats were recovered at the stage of EEG slowing. After sub-serial sectioning, the number and distribution of dying neurons was assessed in each brain region. Acid fuchsin was found to stain moribund neurons a brilliant red. Brains from control rats showed no dying neurons. From 10 to 60 min of cerebral isoelectricity, the number of dying neurons per brain correlated positively with the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min. Neuronal necrosis was found in the major brain regions vulnerable to several different insults. However, within each region the damage was not distributed as observed in ischemia. A superficial to deep gradient in the density of neuronal necrosis was seen in the cerebral cortex. More severe damage revealed a gradient in relation to the subjacent white matter as well. The caudatoputamen was involved more heavily near the white matter, and in more severely affected animals near the angle of the lateral ventricle. The hippocampus showed dense neuronal necrosis at the crest of the dentate gyrus and a gradient of increasing selective neuronal necrosis medially in CA1. The CA3 zone, while relatively resistant, showed neuronal necrosis in relation to the lateral ventricle in animals with hydrocephalus. Sharp demarcations between normal and damaged neuropil were found in the hippocampus. The periventricular amygdaloid nuclei showed damage closest to the lateral ventricles. The cerebellum was affected first near the foramina of Luschka, with damage occurring over the hemispheres in more severely affected animals. Purkinje cells were affected first, but basket cells were damaged as well. Rare necrotic neurons were seen in brain stem nuclei. The spinal cord showed necrosis of neurons in all areas of the gray matter. Infarction was not seen in this study. The possibility is discussed that a neurotoxic substance borne in the tissue fluid and cerebrospinal fluid (CSF) contributes to the pathogenesis of neuronal necrosis in hypoglycemic brain damage.

Role of predation in short-term population fluctuations of some birds and mammals in Fennoscandia.

Abstract: We tested the hypothesis that synchronous fluctuations in small game species in boreal Fennoscandia are caused by varying predation pressure. The main prey of predators are the cyclically superabundant voles. Small game species (alternative prey) are rare compared to voles. The following 4 predictions were checked: (1) Predators should shift their diet from main prey to alternative prey as main prey decline. — This was confirmed using data on red fox (Vulpes vulpes L.) diet.; (2) The mortality rate of alternative prey should be inversely correlated to the abundance of main prey. — This was true for mountain hare (Lepus timidus L.) mortality rates and the rate of nest predation on black grouse (Tetrao tetrix L.).; (3) The total consumption of prey by all the predators should at least equal the critical losses in alternative prey during a decline year. — A tentative estimate of predator consumption amounted to 10 times the losses in grouse and hare.; and (4) The absence of synchrony between the species in the boreonemoral region should be associated with a more diverse diet of predators. — This was the case for red fox diets throughout Sweden. Although all 4 predictions were confirmed, we could not necessarily exclude other hypotheses involving changes in quality or quantity of plant food.

Distribution of neuropeptide immunoreactive nerve terminals within the subnuclei of the nucleus of the tractus solitarius of the rat.

Abstract: The location of substance P, enkephalin and somatostatin (SRIF), and neurophysin II immunoreactive nerve terminals and preterminal processes in the caudal part of the nucleus of the tractus solitarius (nTS) was examined by the indirect immunofluorescence method for immunocytochemistry combined with cytoarchitectural identification of nuclear subgroups in the same tissue. In 22 Sprague-Dawley rats we examined 14-micrometers-thick serial sections of the dorsal medulla at levels from 1 mm caudal to 2 mm rostral to the obex. These sections were incubated with substance P, enkephalin, somatostatin, and neurophysin II antisera. All four peptides were examined in each case and five typical levels (two caudal and three rostral to the obex) were selected for comparison of terminal distribution between peptides. All sections were photographed under the fluorescence microscope and then counter-stained with cresyl violet. This method of analysis revealed distinct patterns of neuropeptide immunoreactivity in the subnuclei of the nTS that varied according to the level of the section. The nTS is responsible for integrating respiratory, cardiovascular (baroreceptor and cardiac), and gastrointestinal functions. The ventrolateral subnucleus (Vl)nTS, ventral subnucleus (v)nTS, interstitial subnucleus (ni)nTS, and intermediate subnucleus (nI)nTS are the major respiratory subnuclei with vlnTS and vnTS prominently associated with pulmonary afferents, ni associated with laryngeal afferents, and nI with tracheal afferents. The vlnTS, vnTS, and ni showed a moderate density of somatostatin-positive nerve terminals, scattered substance P and enkephalin immunoreactivity, and no neurophysin II-positive terminals. The nI showed moderate density of substance P immunoreactive nerve terminals. The subnuclei of the nTS receiving baroreceptor and chemoreceptor afferents--dorsolateral and dorsal (dl and d) subnuclei of nTS--showed scattered substance P immunoreactive nerve terminals. The commissural nucleus of nTS (ncom), which receives most of the cardiac afferents, showed a moderate density of enkephalin-positive immunoreactive nerve terminals. The medial subnucleus (m)nTS at levels rostral to the obex, the primary site for the termination of gastrointestinal afferents, showed substance P immunoreactivity in moderate amounts and weak immunoreactivity for all the other neuropeptides. An important result of these experiments was the observation that regions of the medulla adjacent to the nTS, i.e., the ventral parasolitarius region (vPSR), dorsal (d)PSR, and the periventricular region (PVR) showed the densest amounts of immunoreactive nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Basic Modal Logic

Abstract: It is popular practice to borrow metaphors between different fields of thought. When it comes to evaluating modal logic it is tempting to borrow from the anthropologists who seem to agree that our civilization has lived through two great waves of change in the past, the Agricultural Revolution and the Industrial Revolution. Where we stand today, where the world is going, is difficult to say. If there is a deeper pattern fitting all that is happening today, then many of us do not see it. All we know, really, is that history is pushing on.

Costs of accuracy determined by a maximal growth rate constraint.

Abstract: The present study is best understood as an extension and critique of two schools of thought. The first is that of Malloe and his students, among whom we number ourselves. It is to Maaloe that we are indebted for the idea that logarithmically growing bacteria assemble and use tibosomes in amounts that are optimally adjusted to yield the maximal growth rates supported by different media. Her, we begin our analysis by applying this optimization priciple to all the components of a logarithmically growing system. Our objective is to use the growth optimization constraint as a tool to explore the physiological limits on the accuracy of gene expression. This brings us to our second source of inspiration, which is Orgel's (1963) conception of a problem that Ninio (1982) has referred to as the ‘great error loop’.

The prophenoloxidase activating system in crayfish

Abstract: 1. 1. A preparation (designated 0–40 fraction) containing stable prophenoloxidase (proPO) and other dormant components of the prophenoloxidase activating system was obtained from crayfish hemocytes. 2. 2. Activation of proPO in the 0–40 fraction was elicited by β1,3-glucans, SDS, trypsin or heat, while a protease inhibitor, p-NPGB, inhibited activation of proPO by β1,3-glucans but, not activation by SDS or heat. 3. 3. Ca2+ was always necessary for the activation of proPO and treatment of the 0–40 fraction with EDTA caused irreversible inactivation of proPO activating system, seemingly leaving proPO intact. 4. 4. The enzyme responsible for activating proPO could be separated from proPO and this enzyme was found to be inhibited by p-NPGB. This enzyme could activate proPO in the 0–40 fraction treated with EDTA. 5. 5. Protease activity increased more than 10-fold in the 0–40 fraction after the incubation with β1,3-glucans and Ca2+. 6. 6. The proPO activating system may operate as a recognition system in crayfish, and it is suggested that this system functions as a complement-like system in arthropods.

Elimination of hyaluronic acid from the blood stream in the human

Abstract: The removal of hyaluronic acid (HA) from the blood-stream was studied in four normal human subjects after injection of high molecular weight preparations labelled with 3H in the acetyl position. The plasma half-life of the injected material ranged between 2.5 and 5.5 min. The daily turnover of HA in the circulation was estimated to be at least 150 mg. Its elimination was predominantly extrarenal, the upper molecular weight limit for renal excretion being 25 000. Evidence for rapid degradation was provided by the identification of 3H2O in urine. Calculations from the specific activity of urinary 3H2O indicated that approximately 55% of the acetyl content of the injected HA was completely oxidized within 3 h, and 85% within the first day. It is concluded that hyaluronic acid in the amounts currently used for therapeutic purposes should not accumulate significantly in the circulation.

The Precision of the Conjunctival Provocation Test

Abstract: Repeated conjunctival provocation tests (CPT) were done in 20 children with rhino-conjunctivitis due to birch pollen allergy. Compared with the first open challenge, three successive blinded CPTs were reproducible within an allergen strength difference of one 10-potency in 92% of the tests. Based on the data, a power function was constructed, making it possible to determine the number of patients needed to discriminate CPT sensitivity of a given magnitude between two populations. During the study period specific serum-IgE increased in only three of 19 patients, indicating that stimulation of IgE antibody production is not a common consequence of repeated tests. We conclude that CPT is useful in clinical research. When indicated in clinical routine, CPT is a safe and easy test with good precision.

Potential mobility of phosphorus in different types of lake sediment

Abstract: The fractional composition and potential mobility of sediment phosphorus was investigated in a number of Swedish lakes with different characteristics. Differences between sediments regarding P release patterns in laboratory experiments with varying pH and redox conditions could largely be explained by differences in the fractional composition of the sedimentary P. Sediments from sewage-loaded lakes contained considerably more loosely adsorbed P than unpolluted lakes. P release was redox-sensitive and strongly favoured by high pH values in sediments with a high content of aluminium and iron-bound P. Other sediments released primarily organic and loosely adsorbed P, and in such cases less P was released and redox and pH conditions had less effect. Comparisons with P release rates determined by mass balance calculations were made.

Tissue distribution and retention of 74As-dimethylarsinic acid in mice and rats.

Abstract: The metabolism of dimethylarsinic acid (DMA), a common pesticide and the primary metabolite of inorganic arsenic in mammals, has been studied in mice and rats. About 80% of an oral dose (0.4 mg As/kg body weight) was absorbed from the gastrointestinal tract. In the mice, more than 99% of the dose was eliminated within 3 days, as compared to about 50% in the rats, mainly due to accumulation in the blood. The tissue distribution in the mice was characterized by highest initial (0.5–6 hr) concentrations in kidneys, lungs, intestinal mucosa, stomach, and testes. Tissues with longest retention time were lungs, thyroid, intestinal walls and lens. No demethylation of the74As-DMA to inorganic arsenic was observed, but some of the74As-DMA in the tissues was apparently in a complexed form.

Kinetic impairment of restrictive streptomycin-resistant ribosomes.

Abstract: Comparisons in vivo and in vitro of wild-type and otherwise isogenic bacteria with five different mutant alleles of the gene (rpsL) specifying ribosomal protein S12, all resistant to high levels of streptomycin, show that the streptomycin-resistant (Smr) phenotype can be subdivided into major groups: restrictive and non-restrictive. The restrictive bacteria have a characteristically lower frequency of nonsense suppression in vivo, and are also slower than the wild type in their rate of protein synthesis. Non-restrictive Smr bacteria on the other hand do not differ significantly from the wild type either in nonsense suppression frequencies or in the rate of translation.

Californium-252 plasma desorption time of flight mass spectroscopy of proteins

Abstract: Fast heavy ions, i.e. fission fragments from a 252Cf-source, have been used to desorb and ionize peptides and proteins from a sample surface. Masses of the desorbed ions have been determined by the time-of-flight technique. The mass interval of the molecules studied is 1000-14 000 u. Quasi-molecular ions of higher masses than earlier reported have been observed. The results include the detection of quasi-molecular ions of proinsulins, cytochrome-C, ribonuclease and two phospholipases. The general features of mass spectra of proteins using this ionization method are described. Emphasis is put on the discussion of metastable ion decay, neutral components, multiply charged ions, isotopic broadening, and cluster ion formation. Also the precision which can be obtained with a straight time-of-flight mass spectrometer will be discussed. Future applications of the technique are outlined.

Application of an in vitro assay for serum thymidine kinase: Results on viral disease and malignancies in humans

Abstract: An improved method for the detection of deoxythymidine kinase (TK) in human sera is reported. The method which utilizes 125I-iododeoxyuridine (IdUrd) as a substrate was used to measure TK in sera from patients with different diseases. Sera collected during the acute stage of infectious mononucleosis were found to contain elevated levels of TK, in most cases 10–40 times the normal value. The serum TK activity disappeared gradually and reached a normal level within 4 weeks. Sera from patients with other viral infections contained in most cases normal serum TK levels except in connection with measles, rubella, varicella, herpes simplex virus and cytomegalovirus infections. Additional studies revealed that sera from patients with different types of advanced lymphomas, acute leukemias, chronic granulocytic leukemia and lung cancer of the small-cell type with metastases, contained high TK level which fluctuated in parallel with alterations in activity of the disease. The TK activity in sera from patients with both mononucleosis and tumor disease was characterized by electrophoresis and by its ability to utilize cytidine triphosphate as the phosphate donor. The results showed that the serum TK has the same properties as the human cytosolar TK1, except in connection with varicella.

Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland.

Abstract: The submandibular glands of male rats were exposed to 50 Gy X-irradiation as a single dose, with or without pre-treatment with either alpha-adrenergic agonists (noradrenaline, phenylephrine) or a cholinergic antagonist (atropine). The effects were analyzed by morphometric, cytochemical and biophysical methods. When X-irradiated without drug pre-treatment, many serous epithelial cells of the intralobular convoluted ducts displayed morphologic evidence of irreversible radiation damage, in contrast to neighbouring mucous and other cells which were unaffected. The effect was maximal 96 h after irradiation. Serous cells from animals irradiated after pre-treatment with atropine showed much more wide-spread injury than those of animals exposed to X-irradiation only. In contrast, serous cells suffered considerably less damage if their secretory granules had been depleted 1 or 2 h before irradiation with either noradrenaline or phenylephrine. Other epithelial cells showed no modulation of their slight radioresponsiveness by these drugs. The observations were substantiated by morphometry of three cell types: (a) mucous cells, (b) non-granulated serous and intralobular striated duct cells, and (c) granulated serous cells. The findings suggest that the striking radiosensitivity of salivary gland serous epithelial cells is linked to their content of secretory granules. These granules are rich in heavy metals, as demonstrated cytochemically with the sulphide silver method (SSM). Using particle-induced X-ray emission (PIXE) spectroscopy, the principal metals were shown to be Zn, Mn and Fe. It is conceivable that membranes which enclose organelles rich in metals with the ability to form redox systems (e.g. Fe2+ ai Fe3+) show enhanced sensitity to radiation damage due to the metal-catalyzed induction of lipid peroxidation by ionizing radiation. Disruption of secretory granules would be expected to release lytic enzymes into the cell sap, resulting in autolysis. This hypothesis is supported by the findings that atropine-which increases the number of granulated serous cells-enhances radiosensitivity, while noradrenaline and phenylephrine-which cause degranulation of serous cells-decrease radiosensitivity.

Testing of chemicals for genetic activity with Saccharomyces cerevisiae: a report of the U.S. Environmental Protection Agency Gene-Tox Program.

Abstract: The yeast Saccharomyces cerevisiae is a unicellular fungus that can be cultured as a stable haploid or a stable diploid . Diploid cultures can be induced to undergo meiosis in a synchronous fashion under well-defined conditions. Consequently, yeasts can be used to study genetic effects both in mitotic and in meiotic cells. Haploid strains have been used to study the induction of point mutations. In addition to point mutation induction, diploid strains have been used for studying mitotic recombination, which is the expression of the cellular repair activities induced by inflicted damage. Chromosomal malsegregation in mitotic and meiotic cells can also be studied in appropriately marked strains. Yeast has a considerable potential for endogenous activation, provided the tests are performed with appropriate cells. Exogenous activation has been achieved with S9 rodent liver in test tubes as well as in the host-mediated assay, where cells are injected into rodents. Yeast cells can be recovered from various organs and tested for induced genetic effects. The most commonly used genetic end point has been mitotic recombination either as mitotic crossing-over or mitotic gene conversion. A number of different strains are used by different authors. This also applies to haploid strains used for monitoring induction of point mutations. Mitotic chromosome malsegregation has been studied mainly with strain D6 and meiotic malsegregation with strain DIS13 . Data were available on tests with 492 chemicals, of which 249 were positive, as reported in 173 articles or reports. The genetic test/carcinogenicity accuracy was 0.74, based on the carcinogen listing established in the Gene-Tox Program. The yeast tests supplement the bacterial tests for detecting agents that act via radical formation, antibacterial drugs, and other chemicals interfering with chromosome segregation and recombination processes.

A temperature-sensitive mutant of Escherichia coli that shows enhanced misreading of UAG/A and increased efficiency for some tRNA nonsense suppressors.

Abstract: A spontaneous mutant was isolated that harbors a weak suppressing activity towards a UAG mutation, together with an inability to grow at 43° C in rich medium. The mutation is shown to be associated with an increased misreading of UAG at certain codon contexts and UAA. UGA, missense or frameshift mutations do not appear to be misread to a similar extent. The mutation gives an increased efficiency to several amber tRNA suppressors with-out increasing their ambiguity towards UAA. The ochre suppressors SuB and Su5 are stimulated in their reading of both UAG and UAA with preference for UAG. An opal suppressor is not affected. The effect of the mutation on the efficiency of amber and ochre suppressors is dependent on the codon context of the nonsense codon.