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Biomedical subjects

T Hovig

Publications and source records attributed to T Hovig.

At least 37 records · Page 2Linked to original sources

Studies on the haemostatic defect in a complicated syndrome. An inverse Scott syndrome platelet membrane abnormality?

The Stormorken syndrome is a multifacetted syndrome including a bleeding tendency. No deviations were found in the coagulation- or fibrinolytic systems. Platelet number was low normal, and size abnormal, whereas EM findings were unremarkable. Survival time was half normal. Clot retraction was initially rapid, but clearly decreased, whereas prothrombin consumption was also initially rapid, but complete. Membrane GP's were normal, so was AA metabolism, PI-cycle, granule storage and secretion, and c-AMP function, whereas 5-HT uptake and storage was decreased. Optical platelet aggregation was low normal with all physiological agonists. The only clearly abnormal finding was that coagulant activity was present on non stimulated platelets at the same level as kaolin-stimulated normal platelets. This indicated a platelet abnormality which should lead to a thrombogenic, not to a haemorrhagic trait. This paradox may have its origin in rheology, because when challenged with in vivo shear rates in an ex vivo perfusion chamber, platelet cohesion was abnormally low. Further studies to better delineate the membrane abnormality are underway.

Blood Platelet Disorders↗

Development of granulomas and vascular fibrocellular proliferation in the lungs of pigs receiving long-term lipid-based parenteral nutrition.

The lungs of pigs receiving long-term total parenteral nutrition (TPN) have been studied. A total of 20 pigs were tentatively infused with TPN through central venous catheters for 7 weeks. To secure adequate nutrition and gastrointestinal absorbance of nutrients, an additional full oral diet was given to eight of these animals. Fifteen control animals received Ringer solution through central venous catheters in addition to the oral diet. All animals infused with TPN for 7 weeks developed lung granulomas, a finding not observed in control animals. No lung granulomas were seen in three TPN animals sacrificed after 3 to 5 weeks owing to illness. All TPN animals also developed tissue reactions suggesting long-standing lung vascular inflammation. Similar vascular changes were seen in seven control animals that had bacterial infection or endotoxemia. The total amount of neutral fat in lung homogenate tended to increase in animals given TPN, and the linoleic acid content was significantly increased. In conclusion, long-term TPN caused lung granulomas in pigs. Vascular damage seemed to be accelerated by bacterial infection as well as by the TPN. The tissue reactions presumably involved long-term activation of monocytes/macrophages.

Animals↗

Morphological and functional renal effects of long-term low-dose cyclosporin A treatment in patients with rheumatoid arthritis.

To explore the possible nephrotoxic effects of low-dose cyclosporin A (CyA) treatment, we analyzed the data from 10 patients, aged 35-66 years (mean 51.8 years), who had a clinical diagnosis of rheumatoid arthritis and no known kidney disease. The study protocol included consecutive kidney biopsies and a pretreatment biopsy in all cases. A second biopsy was taken after 5-20 months (mean 17.8 months) of treatment and, in seven patients, a third biopsy was performed after 30-46 months (mean 38.6 months). Evaluation of the kidney biopsies included a semiquantitative estimation of different histological parameters as well as assessment of a chronicity index (CI). Transmission electronmicroscopic examination was performed on all biopsies. There was a significant reduction of glomerular function at the time of both the second (n = 10; p < 0.01) and third (n = 7; p < 0.05) biopsies. Five patients showed an increase in CI on the second biopsy and five on the third biopsy in comparison to pretreatment values. Only one patient showed a progressive increase in CI on three consecutive biopsies. The mean CI increased on both the second (n = 10) and third (n = 7) biopsies compared with baseline, but there was no increase on the third biopsy from the second. The morphological findings were, as a rule, slight or moderate, and focal interstitial fibrosis, tubular atrophy and arteriolar hyalinosis were the most consistent findings. Although even low-dose CyA treatment may be nephrotoxic and may induce morphological alterations in the kidney, such changes do not occur in all patients and may not necessarily be progressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelets in shed mediastinal blood used for postoperative autotransfusion.

Ten patients undergoing open-heart surgery received postoperative autotransfusion of shed mediastinal blood collected in the cardiotomy reservoir. The number, function and morphology of the platelets found in the shed blood were investigated. Platelets were counted using an electronic counter compared with light microscopy. Morphology of platelets was studied with electron microscopy. Platelet aggregation was studied using an aggregometer. Dense granule secretion was measured as the extracellular appearance of adenosine triphosphate. Enumeration of platelets in shed blood using the two methods gave different results. Thus, the electronic counter gave a mean platelet count of 62 x 10(9).l-1, while light microscopy revealed only a mean platelet count of 10 x 10(9).l-1. Electron microscopy disclosed few platelets, but numerous cytoplasmatic fragments smaller than or up to the same size as platelets. The platelets found were mostly shape-changed, spheroid, characterized by centralization and loss of alpha-granules and dense bodies, all changes that indicated irreversible platelet activation. The platelets failed to aggregate in response to the presence of thrombin, adenosine diphosphate or collagen, and secretion of adenosine triphosphate was absent. Plasma from the shed blood was not capable of inducing spontaneous aggregation in platelet-rich plasma from healthy donors. These results indicate that infusion of larger volumes of autotransfused blood should be supplemented with platelet concentrates.

Adenosine Diphosphate↗

Ultrastructural morphometric analysis of human blood platelets exposed to minimal handling procedures.

A detailed morphometric study of normal human blood platelets is described. The purpose has been to evaluate the morphological characteristics of platelets exposed to minimal handling procedures in order to obtain an optimal basis for the appraisal of platelets in disease. Blood from 10 healthy volunteers was collected directly into buffered glutaraldehyde and processed for electron microscopy. This platelet fixation procedure resulted in excellent preservation of resting platelet ultrastructure with one exception: the dense bodies. Compared to platelets fixed following washing procedures, our directly fixed platelets comprised fewer pseudopods and contained more glycogen. An unexpected feature of the open canalicular system was the apparent release of blisters interpreted as microvesicles. Employing a computerized image analyzer, 300 of the platelets were examined morphologically. The morphometric data thus obtained were analyzed statistically, resulting in a set of standard values for morphological characteristics of human platelets which we have found useful in subsequent evaluations of platelet morphology in disease. Significant inter-individual variance was, however, detected in two instances, in the section area of the alpha granules, as well as the area fraction of platelet sections occupied by channels of the open canalicular system (OCS). This should be taken into consideration when appraising platelet ultrastructure in health and disease.

Adult↗

Studies of autacoid responsiveness and endothelium dependency in human umbilical arteries.

The effect of serotonin, prostaglandin E2 (PGE2) and PGF2 alpha on the smooth muscle tension in perfused human umbilical arteries was investigated before and after removal of the endothelium. Denudation was performed mechanically using a nylon filament loop, and the efficiency of the procedure was checked by electron microscopy. In non-denuded vessels the autacoids elicited biphasic pressure responses, all starting with a vasodilatation and followed by a strong vasoconstriction. After denudation no dilatatory responses were evoked, whereas the constrictory responses appeared to be unchanged. Pre-treatment of the vessels with methylene blue did not affect the autacoid responses. Generally the perfusion pressure decreased after the de-endothelialization, in some preparations to levels of about 50% of the initial perfusion pressure. In about one-third of the preparations exposure to methylene blue led to a definite pressure increase. The results indicate that endothelium-derived factors are involved in the autacoid responses and also in the maintenance of basic vascular tonus in the umbilical circulation.

Autacoids↗

Platelets and vitronectin: immunocytochemical localization and platelet interaction with exogenously added vitronectin.

Vitronectin stores were localized in human platelets by immunofluorescence, confocal laser microscopy, and immunoelectron microscopy. In ultrathin cryosections, the immunogold labelling was mainly observed in the alpha-granules, although occasional immunolabelling of the platelet surface was present. The interaction between thrombin-stimulated platelets and exogenously added vitronectin was also explored. This vitronectin had been purified by heparin-affinity chromatography. Binding of vitronectin to thrombin-stimulated platelets was demonstrated by flow cytometry. The immunoelectron microscopical studies revealed that this binding was mainly restricted to clumps of released alpha-granular material on the platelet surface. The possible significance of the interaction between exogenous vitronectin and released platelet proteins is discussed.

Amino Acid Sequence↗

Sera from preeclamptic women increase the content of triglycerides and reduce the release of prostacyclin in cultured endothelial cells.

UNLABELLED: The causes of the "endothelial dysfunction" accompanying preeclampsia are unknown. Women with preeclampsia have a marked hyperlipidemia which reflects altered lipid metabolism. We asked if the hyperlipidemic sera of preeclamptic women could cause altered endothelial cell properties. Cultured endothelial cells were incubated with sera from women with preeclampsia (PE) or normal pregnancies as controls. Fifty PE-sera were tested and in 45 cases the endothelial cells acquired a large number of sudanophilic granules which by electron microscopy had lipid appearance. In 31 incubations with 31 individual control sera cellular lipid granules were observed in 4 cases. The cellular triglyceride content was increased to 153 +/- 30 compared to 48 +/- 10 micrograms/mg cell protein in the control cells. Furthermore, the endothelial release of prostacyclin, measured as 6-keto PGF1 alpha, was 8.8 +/- 0.6 ng/mg cell protein in cells incubated with PE-sera as compared to 40.3 +/- 6.4 ng/mg in the control cells. CONCLUSION: The hyperlipidemic sera from preeclamptic women induced triglyceride accumulation in cultured endothelial cells. This was accompanied by altered endothelial function as demonstrated by reduced prostacyclin release.

6-Ketoprostaglandin F1 alpha↗

X-linked thrombocytopenia and thrombocytopathia: attenuated Wiskott-Aldrich syndrome. Functional and morphological studies of platelets and lymphocytes.

Detailed studies on the rare disorder X-linked thrombocytopenia showed that it resembles the Wiskott-Aldrich syndrome (WAS) in inheritance, clinical bleeding tendency, platelet morphology, marked thrombocytopenia and microplatelets. The calculated platelet mass was 5% of normal. Functional and biochemical studies indicated qualitatively normal aggregation and release mechanisms, whereas a moderate storage pool defect was present. The classical platelet membrane glycoproteins and lymphocyte sialophorin (CD 43) were normal. The reason for the bleeding tendency was concluded to be deficient hemostatic plug formation resulting from the low platelet mass and a moderate storage pool defect. The only clear distinction from WAS was the normal immunofunctional tests, the moderate tendency to infections and the absence of eczema. We therefore consider the trait as an attenuated form of WAS. That women are affected may indicate a particular variant.

Adenosine Diphosphate↗

Subdural compartment in pig: a morphologic study with blood and horseradish peroxidase infused subdurally.

The dura-arachnoid junction is examined in normal animals and in animals subjected to subdural infusion of blood immediately prior to death, simulating acute subdural hemorrhages. The Norwegian landrace pig is used as the experimental animal. Horseradish peroxidase (HRP) has been added to the injected blood to serve as a macromolecular tracer. The material is studied by light and electron microscopy. Special attention is given to the level of the induced subdural cleavage plane, the total distribution of the infused blood, and the natural sites of drainage. The dura-arachnoid junction, identified here as the subdural compartment (the dural border layer of others), consists of an avascular tissue with flake-like, relatively electron-lucent cells stacked upon each other in several layers with narrow intercellular clefts. Under normal conditions there is no evidence of a so-called "subdural space." When under the present experimental conditions bleeding takes place into this cellular tissue, it splits without any particular, predestined cleavage plane, although most often close to the fibrous matter of the dura. The bleeding extends throughout the cerebral and spinal parts of the compartment and also along the spinal nerve roots. Contamination of the subarachnoid space occurs only in some cases subjected to large infusions and apparently only at spinal levels. The HRP diffuses into the dura, but does not traverse the arachnoid barrier layer.

Animals↗

Acute morphological changes in canine kidneys after exposure to extracorporeal shock waves. A light and electron microscopic study.

The acute effects of extracorporeal shock waves on renal morphology were studied by light and electron microscopy in 14 dogs. One kidney received an average clinical number of exposures, the nonexposed, contralateral kidney serving as control. The original Dornier HM-3 generator was used in 3 animals, the modified version in 11. Intravascular radiographic contrast medium was administered in five animals. Damage was observed in all exposed kidneys, none in the contralateral control kidney. The effects were characterized by renal and perirenal hemorrhage and edema, parenchymal hemorrhagic foci with tissue destruction, often extending from cortex to medulla. In the nearby regions there was endothelial cell damage in arteries, veins and glomerular capillaries. Breaks in the wall of these vessels were detected with platelet plug formations and thrombi. In glomeruli, breaks of Bowman's capsule and epithelial cell damage with loss of foot processes were observed. A wide range of tubular cell damage was demonstrated, ranging from vacuolization to complete necrosis. Tubular lumina were filled with red cells, indicating renal origin of hematuria. The tissue damage was less pronounced in kidneys exposed to the modified lithotriptor than to the original. No difference in the quantity or quality of damage was detected whether radiographic contrast medium was administered or not.

Animals↗

Renal failure in adult patients with hereditary tyrosinaemia type I.

An adult patient with hereditary tyrosinaemia type I who developed renal failure is reported. She received a renal transplant at the age of 23 years. In childhood her kidney disease was dominated by multiple tubular defects with resulting hypophosphataemic rickets. Metabolic acidosis was the most prominent feature in the years preceding the transplantation. Her kidneys were contracted to 40 g. The major morphological finding was that of a tubulointerstitial nephropathy. Liver biopsies taken at the ages of 5.5 and 23 years showed cirrhotic changes. Crystalloid inclusions in the liver mitochondriae were a prominent finding on electron microscopy. Fumarylacetoacetase was deficient in liver, kidneys, fibroblasts and lymphocytes. The typical biochemical parameters of tyrosinaemia, succinylacetone, p-hydroxyphenyllactate, p-hydroxyphenylpyruvate and serum tyrosine were only slightly elevated. A brief history of a second adult tyrosinaemia patient with decreasing renal function is also given.

Adolescent↗

Epithelial cells from human fallopian tube in culture.

The epithelial cells lining the inner surface of the Fallopian tube influence the reproductive process by both their ciliary and secretory activities. The aim of the present work was to establish a method to culture these cells as a model for more specific studies of their properties. Minor slices of the mucosal ridges were cut and minced extensively using a fine scissor. The resulting pieces were washed once, resuspended in RPMI 1640 with 20% fetal calf serum and seeded in plastic dishes. After 2 days, the medium was replaced with RPMI 1640 containing human albumin, insulin and transferrin. Seven to 10 days later, the cell number had increased 5-8 times in 70% of the cultures. The identity of the cells was assessed after 1-3 weeks in culture. Of the cells, 98% stained positive for the antibody to epithelial cell-specific protein cytokeratin. Electron microscopic studies of the cultures showed epithelial characteristics including cilia, microvilli and intercellular junctions in the form of desmosomes. The cells could be kept in culture for 6-8 weeks. In conclusion, a method to culture epithelial cells from the human Fallopian tube is described. The cells have been identified and they can be kept in culture for 6-8 weeks in quantities sufficient for experimental use.

Cells, Cultured↗

Studies on a patient with thrombocytopenia, giant platelets and a platelet membrane glycoprotein Ib with reduced amount of sialic acid.

A 70-year-old patient with a life-long bleeding tendency, giant platelets and thrombocytopenia (10-40 x 10(9) platelets/l) has been studied. This is a condition often associated with lack of platelet membrane glycoprotein Ib (GP Ib). Electron microscopy of fixed platelets incubated with monoclonal antibodies to GP Ib (AN 51, AP 1) and gold-labelled goat anti-mouse IgG, showed a distinct distribution of GP Ib on the patient's platelets, however. Crossed immunoelectrophoresis and SDS-PAGE demonstrated a reduced mobility of the patient's GP Ib which could be explained by absence of sialic acid. Blotting with peroxidase-conjugated peanut agglutinin confirmed this conclusion. This lectin binds to galactose-N-acetyl-galactosamine residues exposed terminally when sialic acid is absent from the carbohydrate side-chains. Such binding could be seen with normal GP Ib only after neuraminidase treatment. Fluorescence studies with FITC-conjugated peanut agglutinin showed binding of the lectin to intact patient platelets, indicating that lack of sialic acid was not introduced during the platelet isolation procedure. Neither could the lack of sialic acid be attributed to increased neuraminidase activity as studied in vitro. Platelets treated with neuraminidase in vivo or in vitro are rapidly cleared from the circulation. Therefore the patient's thrombocytopenia may be associated with the reduced amount of GP Ib sialic acid. As far as we know, similar cases have not been described previously.

Aged↗

Emery-Dreifuss syndrome in three generations of females, including identical twins.

Emery-Dreifuss syndrome is characterized by early contractures, slowly progressing muscle wasting and cardiomyopathy, often presenting as heart block. The syndrome is usually inherited as an X-linked recessive. We present a family with four affected females in three generations, including a pair of identical twins. All patients developed elbow contractures, scoliosis, and stiffness of the spine and neck from the age of about 10, with little progression in later years. The proband developed cardiomyopathy at the age of 45, whereas her mother died at 41 without a confirmed diagnosis of cardiomyopathy. The twin daughters of the proband had no unequivocal signs of cardiomyopathy at the age of 21 years. Early recognition of this syndrome is important because of the possible development of heart block.

Adult↗

Characterization of a new malignant human T-cell line (PFI-285) sensitive to ascorbic acid.

A new malignant human T-cell line-labelled PFI-285-has been isolated from a boy with malignant lymphoma. Morphologically, the cells had characteristics of malignant lymphoid cells. The cells presented surface antigens as early cortical lymphocytes and proliferated non-adherently as single cells, independent of T-cell growth factor (IL-2), in liquid culture. The cells had undetectable levels of receptors for IL-2, were not clonogenic in soft agar, but did form tumors in nude mice. Their establishment and continuous growth in vitro was dependent on the number of cells inoculated and on the growth medium used. Cytogenetic alteration, HTLV-1 or reverse transcriptase activity were not detected. The production of known T-cell derived lymphokines such as IL-2, B-cell growth factor(s), alpha-interferon or granulocyte/macrophage colony stimulating or inhibiting factor(s) was not detected. The cells had 5-8% natural killer (NK)-cell activity against NK-cell sensitive target cells (K562) and were not sensitive for NK cells. A most unusual characteristic was the pronounced sensitivity of the cells to ascorbic acid. Concentrations down to 50 mumol/l killed the cells within hours.

Adolescent↗

The influence of fixation on the relative amount of cytoplasmic ribosomes in mouse epidermal basal keratinocytes. A morphometric study of so-called "dark cells" and their putative role in epidermal carcinogenesis.

The nature and significance of so-called dark keratinocytes in the epidermis during chemical carcinogenesis is still a matter of concern and debate. Based on ultrastructural observations it has been suggested that dark cells most often are shrunken cells. Reports on skin carcinogenesis, however, claim that dark cells are a sign of ongoing tumor promotion and represent those stem cells in the epidermis from which the tumors originate. It is therefore important to find out whether these cells are simply injured and shrunken cells, or vital cells of great importance for carcinogenesis. Dark cells are assumed to be rich in ribosomes. There is evidence, however, that the observed number of dark cells is highly dependent on tissue fixation. In the present ultrastructural study, morphometric methods were used to compare the effects of two different fixation procedures on the amount of cytoplasmic ribosomes in dark cells from both untreated and carcinogen-treated hairless mouse epidermis. The results show that the ultrastructural features of both dark and clear cells vary considerably with different fixation procedures. In acetone-treated controls typical dark cells are only observed when the fixative has a lower osmotic activity than the plasma. With iso-osmolal fixation typical dark cells are not observed. After an abortive two-stage carcinogenesis treatment, in which a single application of 9,10-dimethyl-1,2-benzanthracene (DMBA) in acetone was followed by a single application of 12-O-tetradecanoyl-13-acetate (TPA) in acetone, signs of cell injury could be found after both fixation procedures. With DMBA/TPA and hypo-osmolal fixation the number of dark cells seemed to increase, whereas only signs of cell injury with occurrence of some heavily altered "clear cells" dominated the picture with iso-osmolal fixation. Morphometry showed that both the numerical and the volumetric densities of cytoplasmic ribosomes in basal keratinocytes varied most significantly with the fixation procedure used. The cytoplasmic volumes did not vary in a way that could explain these differences. One might therefore assume that the number of ribosomes depends on the fixative. Large swelling artifacts occurred when a fixative with low osmotic activity was used, leading to compression of neighboring cells. Hence, an increased ribosomal density reported previously in dark cells is probably related to such cell volume artifacts and does not reflect an actually increased quantity of ribosomes.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗