Showing papers by "Uppsala University published in 1983"

Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus.

Abstract: A partial amino acid sequence of human platelet-derived growth factor, the major mitogen in serum for cells of mesenchymal origin, has been determined. A region of 104 contiguous amino acids shows virtual identity with the predicted sequence of p28sis, the putative transforming protein of simian sarcoma virus (SSV). This similarity suggests a mechanism for transformation by SSV and other agents, involving expression of growth factors.

Imaging dopamine receptors in the human brain by positron tomography

Abstract: Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans.

Instrumental Variable Methods for System Identification

Abstract: This paper gives a tutorial overview of instrumental variable methods. Comparisons are made to the least-squares method. An analysis including consistency and asymptotic distribution of the parameter estimates is included.

NADPH‐diaphorase: A selective histochemical marker for striatal neurons containing both somatostatin‐ and avian pancreatic polypeptide (APP)‐like immunoreactivities

Abstract: Certain neurons in the brain are specifically and intensely stained by a histochemical method which demonstrates nicotinamide adenine dinucleo-tide phosphate NADPH-diaphorase activity. The cell types containing this enzyme in certain areas of the rat forebrain were examined by combining NADPH-diaphorase histochemistry with the indirect immunofluorescence technique. Neurons containing somatostatin- or avian pancreatic polypep-tide (APP)-like immunoreactivities were found throughout the forebrain including the striatum and neocortex. These two neuropeptides were also found to coexist in many telencephalic neurons. After photography, the sections processed for immunohistochemistry were stained for NADPH-diaphorase activity by a histochemical method. It was found that within the striatum all of the neurons that were selectively stained by this technique also contained both somatostatin- and APP-like immunoreactivities. Also in the neocortex NADPH-diaphorase was found only in those neurons displaying somatostatin- or APP-like immunoreactivity. In other brain regions such as the nucleus laterodorsalis tegmenti, NADPH-diaphorase-containing cells did not contain these neuropeptides. The results indicate that NADPH-diaphorase histochemistry provides a simple, reliable, histochemical method to demonstrate those striatal neurons in which somatostatin- and APP-like immunoreactivities coexist. The selective occurrence of this enzyme within these neurons may provide a useful target for pharmacological studies of these neuropeptide-containing cells.

Dynamics of the Relaxation-Time Spectrum in a CuMn Spin-Glass

Abstract: SQUID magnetometry measurements on a $\mathrm{Cu}\mathrm{Mn}$ spin-glass reveal that the zero-field-cooled magnetization strongly depends on the time the sample is kept at constant temperature prior to the field application. This result is evidently at variance with the common belief that an equilibrium spin-glass state is quickly obtained after cooling in zero field. The nonequilibrium behavior, as reflected in the complex time dependence of $\frac{\ensuremath{\partial}m}{\ensuremath{\partial}\mathrm{ln}t}$, is interpreted to arise from slow dynamics of the relaxation-time spectrum.

HLA-D region β-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals

Abstract: The human HLA-D histocompatibility region encodes class II antigens each of which consists of two polypeptide chains (α and β) inserted in the plasma membrane. These molecules are implicated in the regulation of the immune response1-3 but several human diseases are also found to be associated with certain HLA-DR antigens4. The occurrence of insulin-dependent (type I) diabetes (IDDM) is strongly associated with HLA-DR3 and/or 4 (ref. 5). The class II antigens, however, show a marked genetic polymorphism1 associated with the β-chains6,7 which seem, from hybridization studies, to be encoded by several genes8,9. We have therefore used the β-chain cDNA probe, pDR-β-1 (refs 8, 10) to test whether there are differences in hybridization pattern between DNA from healthy individuals and diabetic patients, after digestion with restriction endonucleases. Among the HLA-DR 4 and 3/4 individuals, the IDDM patients showed an increased frequency of a PstI 18 kilobase (kb) fragment. A BamHI 3.7 kb fragment, frequent among controls (30-40%), was rarely detected in the IDDM patients (0-2%). These differences may be related to susceptibility to develop the disease. (Less)

Induction of degranulation and lysis of haemocytes in the freshwater crayfish, Astacus astacus by components of the prophenoloxidase activating system in vitro.

Abstract: To study the role of the prophenoloxidase activating system, an enzyme cascade located in the haemocytes of crustaceans, in the cellular defences of the freshwater crayfish, Astacus astacus in vitro, monolayer cultures of mixed or separated haemocyte populations, isolated by density gradient centrifugation, were challenged with the bacterium, Moraxella sp. pre-coated with phenoloxidase and the other attaching proteins in crayfish haemocyte lysate (HLS), or in the case of controls, with saline or Moraxella sp. pre-incubated in saline alone. Examination of the coverslips 1 h after inoculation revealed that, in the mixed haemocyte cultures, most of the cells had undergone profound degranulation and lysis following exposure to the HLS-coated bacteria. Cell lysis was also evident in the experimental semigranular cell monolayers, but not in the controls, although in those controls treated with the saline-incubated bacteria, the semigranular haemocytes had undergone degranulation without lysis. In contrast, the granular cells appeared to be unaffected by the saline-incubated Moraxella sp., and with the HLS-coated bacteria displayed only marked degranulation. Greater numbers of bacteria were always associated with the cells or cell remnants in the experimental cultures compared to the controls. We suggest that the attaching proteins of the prophenoloxidase cascade are strong nonself signals for the haemocytes, causing them to degranulate and release previously cell-bound recognition factors into the haemolymph, where they are free to trigger activation of adjacent haemocytes.

Stimulation by glucose of the blood flow to the pancreatic islets of the rat.

Abstract: Blood flow to the pancreatic islets of the rat was estimated with the microsphere technique. Experiments with microspheres of different sizes (diameter 10, 15 or 50 micron) showed that optimal results were obtained with 10-micron spheres. Localization of microspheres either within or outside the islets was accomplished by freeze-thawing of the pancreas, making it transparent, so that both islets and microspheres could be distinguished in dark field illumination. Thus, microscopic examination of the freeze-thawed pancreas allowed the microspheres to be counted separately in both the endocrine and exocrine parenchyma. Under basal conditions, pancreatic blood flow was calculated as 0.60 ml X min-1 X g-1 (w/w). The islets accounted for about 10% of the total pancreatic blood flow, corresponding to 0.069 ml/min per whole pancreas. A bolus dose of glucose increased pancreatic blood flow to 0.75 ml X min-1 X g-1 (p less than 0.05), while the fractional islet blood flow rose to 15.1% (p less than 0.001) corresponding to 0.125 ml X min-1 X pancreas-1 (p less than 0.001). The glucose-induced increase in pancreatic blood flow mainly resulted from increased flow to the pancreatic tail, while the corresponding increase in islet blood flow was uniformly distributed throughout the pancreas. Injection of the non-metabolizable glucose-derivate. 3-0-methyl-D-glucose, affected neither the pancreatic nor the islet blood flow. The data indicate that the islets receive more of the pancreatic blood flow than would be accounted for by their relative volume and that glucose preferentially stimulates blood flow to the islets.

Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP.

Abstract: The two enantiomers of the putative centrally acting dopamine (DA) autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP (Hjorth et al. 1981), were pharmacologically evaluated. An extensive series of biochemical and behavioural experiments unexpectedly revealed that both (+)- and (-)-3-PPP showed clear, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA agonist with autoreceptor as well as postsynaptic receptor stimulatory properties. In contrast, although (-)-3-PPP similarly activates DA autoreceptors it acts concomitantly as an antagonist at postsynaptic DA receptors. Moreover, both behavioural and biochemical data on motor activity and DA synthesis and turnover suggest a preferential limbic action for the (-)-enantiomer. These results are discussed in terms of the dual antidopaminergic action of (-)-3-PPP coupled with anatomical differences in the feedback organisation in central (viz, limbic vs striatal) DA systems. It is suggested that compounds like (-)-3-PPP may be of potential clinical utility in the treatment of psychotic disorders, whilst lacking the seriously incapacitating motor dysfunctions produced by current neuroleptic therapy.

Role of extradural and of general anaesthesia in fibrinolysis and coagulation after total hip replacement

Abstract: Thirty patients undergoing total hip replacement were randomly allocated to one of two groups. One group (n = 14) received extradural anaesthesia with 0.5% bupivacaine with adrenaline continued into the postoperative period (24 h) for pain relief. The other group (n— 16) received general anaesthesia with controlled ventilation, using nitrous oxide in oxygen and fentanyl i.v. Following surgery they received a narcotic analgesic i.m. on demand. Analysis of fibrinolysis inhibition activity and plasminogen activators revealed a significantly better fibrinolytic function in patients given continuous extradural anaesthesia than in those who received general anaesthesia followed by narcotics in the period after operation. Furthermore, the capacity for activation of factor VIII was significantly lower after operation in the former group.

Codon-specific missense errors in vivo.

Abstract: We have developed a simple method for measuring the missense substitution of amino acids at specified positions in proteins synthesized in vivo We find that the frequency of cysteine substitution for the single arginine in Escherichia coli ribosomal protein L7/L12 is close to 10(-3) for wild-type bacteria, decreases to 4 x 10(-4) in streptomycin-resistant bacteria containing mutant S12 (rpsL), and is virtually unchanged in Ram bacteria containing mutant S4 (rpsD) We have also found that the frequency of the cysteine substitution for the single tryptophan in E coli ribosomal protein S6 is 3-4 x 10(-3) for wild-type bacteria, decreases to 6 x 10(-4) in streptomycin-resistant bacteria and is elevated to nearly 10(-2) in Ram bacteria

Epidermal Growth Factor Modulates Thyroid Growth and Function in Culture

Abstract: The effect of epidermal growth factor (EGF) on the growth and function of porcine thyroid follicle suspension cultures was examined. When incubated with EGF (0.01–10 ng/ ml), the incorporation of [3H]thymidine was markedly stimulated, with the half-maximal effect occurring at about 0.5 ng/ ml. Through 6-day experiments, [3H]thymidine incorporation increased almost linearly after an initial lag phase of 1 day. Autoradiographical analysis showed that more than 50% of the nuclei were labeled after 4 days of incubation with EGF (10 ng/ ml) compared to control values of 3–7% labeled nuclei. EGF was essentially as effective in serum-free medium as in medium containing 1% fetal calf serum. EGF added at the same concentrations that stimulated incorporation of [3H]thymidine was found to reduce iodide metabolism of the follicles within 30 min of addition; both TSH-stimulated efflux and organification of [125I] iodide were suppressed by the addition of EGF. Since EGF is a physiologically occurring substance, the dat...

Estimating Bacterioplankton Production by Measuring [3H]thymidine Incorporation in a Eutrophic Swedish Lake

Abstract: Bacterioplankton abundance, [3H]thymidine incorporation, 14CO2 uptake in the dark, and fractionated primary production were measured on several occasions between June and August 1982 in eutrophic Lake Norrviken, Sweden. Bacterioplankton abundance and carbon biomass ranged from 0.5 × 109 to 2.4 × 109 cells liter−1 and 7 to 47 μg of C liter−1, respectively. The average bacterial cell volume was 0.185 μm3. [3H]thymidine incorporation into cold-trichloroacetic acid-insoluble material ranged from 12 × 10−12 to 200 × 10−12 mol liter−1 h−1. Bacterial carbon production rates were estimated to be 0.2 to 7.1 μg of C liter−1 h−1. Bacterial production estimates from [3H]thymidine incorporation and 14CO2 uptake in the dark agreed when activity was high but diverged when activity was low and when blue-green algae (cyanobacteria) dominated the phytoplankton. Size fractionation indicated negligible uptake of [3H]thymidine in the >3-μm fraction during a chrysophycean bloom in early June. We found that >50% of the 3H activity was in the >3-μm fraction in late August; this phenomenon was most likely due to Microcystis spp., their associated bacteria, or both. Over 60% of the 14CO2 uptake in the dark was attributed to algae on each sampling occasion. Algal exudate was an important carbon source for planktonic bacteria. Bacterial production was roughly 50% of primary production.

Immunocytochemical identification of polypeptide YY (PYY) cells in the human gastrointestinal tract.

Abstract: Various parts of the human gastrointestinal tract were investigated immunocytochemically for the occurrence of polypeptide YY (PYY) and pancreatic polypeptide (PP). PYY-immunoreactive cells were observed in the lower part of the ileum, in the colon and in the rectum, and PP-immunoreactive cells were found in the colon and rectum. Both cell types were of the open type, i.e. they extended from the basal lamina to the gut lumen. PYY-immunoreactive cells were seen to emit cytoplasmic processes to the neighbouring goblet cells. This latter observation suggests that PYY cells may exert a paracrine action on the mucussecreting goblet cells. Staining of consecutive thin plastic sections and staining of the same section simultaneously for two peptides showed that PYY-immunoreactivity did not occur in PP- or enteroglucagon-immunoreactive cells. On the ultrastructural level PYY-immunoreactivity was localized in basal granulated endocrine cells. These cells contained round or slightly oval electron dense granules with a mean diameter of 150 nm (range 100–300 nm).

Perceptual, motor and attentional deficits in Swedish primary school children. Some child psychiatric aspects.

Abstract: One hundred and forty-one seven-year-old children took part in an extensive neuropsychiatric study. Eight-two of these children had been selected and sampled from a group of 3448 children for whom questionnaires concerning motor control, perception and attention/behaviour had been completed by pre-school teachers. They all showed pre-school signs of both attention deficit and motor/perception dysfunction. The fifty-nine remaining children had been randomly sampled from the group of 3448 children to serve as controls. The study was carried out in a blind fashion. The present paper reports on results of the neuropsychiatric study with special regard to psychiatric disorders in so-called MBD syndromes, defined in accordance with operational criteria. Prevalence figures for marked psychiatric abnormality in MBD were shown to be higher than for psychiatric abnormality in children with 'neuroepileptic' disorders in the Isle of Wight study. Psychotic behaviour was found to be specifically associated with MBD. Hereditary and neuropathogenic factors singly or together possibly caused the 'MBD handicap'. Non-optimal psychosocial factors appear to interact with the MBD syndrome in the moulding of psychiatric disorders.

The effect of platelet-derived growth factor on morphology and motility of human glial cells

Abstract: Platelet-derived growth factor (PDGF) is a mitogen for several cell types in culture. It is documented in this work that one of the earliest effects of PDGF on serum-starved glial cells is an induction of intensive motile activity. Within the first minute after the addition of PDGF thin membrane lamellae grow out around almost all of the cell circumference. Later, circular arrangements of small ruffles appear on the dorsal surface of the cells. These rings of ruffles vary in size and some encircle almost the whole cell. The organization of the peripheral weave of microfilaments in the PDGF-induced advancing lamellae was closely similar to that of normally growing cells. In the regions of the circular arrangements of ruffles there was an extensive reorganization of the surface actin with unusual arrangements of microfilament bundles and polygonal networks. There was also a general intensification of the translocation of membrane ruffles and spikes from the cell periphery towards the centre of the cell, increased micropinocytotic activity and shuttling of intracellular particles.

Physiology of the choroidal vascular bed

Abstract: The choroidal vascular bed has many interesting features such as relatively wide but flat capillaries, fenestrated capillary walls and an enormous blood flow. The high flow rate results in a high oxygen tension in the tissue and is also of importance in the temperature control of the eye. The capillary wall is permeable to plasma proteins which is probably of great importance for the supply of vitamin A to the pigment epithelium. The permeability to low molecular weight substances is very high which results in a tissue fluid similar to plasma with respect to small molecules. It is not clear whether the choriocapillaris is normally reabsorbing fluid transported into the choroid from the retina and from the anterior chamber or if there is a net filtration from the choriocapillaris. Fluid can pass from the choroid through the suprachoroid into the episcleral tissues via the scleral substance and spaces around the blood vessels and nerves.

An improved environmental index based on the relative abundance of oligochaete species

Abstract: Howmiller & Scott (1977) presented an ‘Environmental Index’ based on thorough knowledge of the ecological demands of species of freshwater oligochaetes frequently found in North American waters. These authors emphasized the fact that common diversity measures do not utilize information about the ecological attributes of the constituent species but rather about community structure. A modification of the ‘Environmental Index’ is here presented with the aim of increasing its sensitivity in Europe and possibly also in North America. Four ecological groups are here preferred to the original three, and the ecological valence of the ‘key-species’ Tubifex tubifex is discussed at some length. Whereas most environmental and diversity indices remain little affected by changes in the total abundance of oligochaetes, the modified index is sensitive to such changes. Comparisons are made with two of the most popular diversity indices applied to specific situations, i.e. the Shannon-Weaver index and Simpson's index.