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Biomedical subjects

S Schulman

Publications and source records attributed to S Schulman.

At least 163 records · Page 9Linked to original sources
PubMed1985

Rhoptry secretion of membranous whorls by Plasmodium berghei sporozoites.

Electron microscopy of sporozoites of the rodent malaria parasite, Plasmodium berghei, reveals electron-dense multilaminate membranous whorls within components of the rhoptry-microneme complex after fixation with tannic acid in conjunction with glutaraldehyde. This multilaminate material, which has a dark line to dark line periodicity of approximately 5 nm, appears to be secreted from the sporozoite since it is also found adhering to the sporozoite's external surface. The material may function in sporozoite gliding motility and in invasion of host cells.

Animals↗
PubMed1985

Factors and inhibitors of blood coagulation and fibrinolysis in acute nonlymphoblastic leukaemia.

Factors of coagulation and fibrinolysis have been evaluated in 15 patients with untreated acute nonlymphoblastic leukaemia (ANLL). 10 patients had major bleeding (MB) and 6 had laboratory signs of DIC. 5 patients went into complete remission (CR). Antithrombin III (AT III) was decreased in 7 patients, antiplasmin (AP) in 9, fibronectin (FN) in 6 and factor XIII in 4/12. The ratio between factor VIIIR:Ag and factor VIII:C was over 2.0 in 11 patients, and high values were especially seen in patients with MB and patients with DIC. Spontaneous proteolytic activity, measured with S-2288 was increased in 3 patients who all had MB, and none of whom achieved CR. 2 patients with promyelocytic leukaemia (M3) had low fibrinogen and AP, high FDP and normal AT III, speaking for primary fibrinolysis, which in addition to proteolytic enzymes in the blast cells are important contributing factors regarding MB in ANLL.

Adult↗
PubMed1985

Role of the carbohydrate domains of glycophorins as erythrocyte receptors for invasion by Plasmodium falciparum merozoites.

Solubilized preparations of purified glycophorins and specific domains of these molecules were assessed for their effects as inhibitors of Plasmodium falciparum invasion of human erythrocytes in vitro. The ability of newly invaded merozoites to continue developing and incorporating [3H]hypoxanthine during a 24-h period after their invasion was used as an assay for merozoite invasion. Glycophorins A, B, and C were found to be equally effective as inhibitors. Previous studies had shown N-acetylglucosamine, a sugar component of glycophorins A and C but not B, to be an effective inhibitor. Accordingly, molecular domains common to all of the glycophorins were further assessed. Sialic acid was shown to act almost as effectively as N-acetylglucosamine, presumably because of the structural similarities between these sugars. The inhibitory ability of sialic acid is considerably enhanced when presented to the parasite in a clustered form, as in an oligosaccharide. The acetyl group of these sugars does not appear to play an essential role in this inhibition. How the P. falciparum merozoite recognizes and interacts with the sugar domains of the glycophorin molecule remains to be determined.

Animals↗
PubMed1985

Studies on the medical treatment of deep vein thrombosis.

The aim of these studies was to investigate different regimens of thrombolytic therapy and oral anticoagulation, and to evaluate the effects of streptokinase (SK), heparin and warfarin in the treatment of deep vein thrombosis (DVT). Low-dose SK, although controlled according to the fibrinogen levels, did not provide improved thrombolysis compared to conventional high-dose SK, and more postthrombotic changes were registered after an average of 3 years. Furthermore, serious hemorrhagic side-effects occurred, which makes this regimen inexpedient. Various regimens of local venous infusion of SK were tried, and with a dose of 4,000 IU/h for 72 h in combination with heparin a thrombolytic effect was achieved, albeit not greater than usually observed with conventional SK. Systemic hypofibrinogenemia and hemorrhage were not avoided. A hitherto not described side-effect with bullous dermatitis was reported. Venographic severity of calf vein thrombosis displayed a statistically significant correlation to long-term hemodynamic changes, as assessed with foot volumetry, after an average of 5 years. This correlation was stronger for the size of the thrombus after initial treatment than for the size at diagnosis. Thus it seems important to treat calf vein thrombosis with heparin in order to limit the extent of the thrombus, thereby reducing long-term sequelae. During heparin treatment, an average reduction of the thrombi of 17% was observed. This reduction was significantly correlated to a short duration of symptoms but not to parameters of heparin therapy or fibrinolytic components. However, patients with substantial thrombolysis had high plasmin-alpha 2-antiplasmin (PAP) levels, and those with high tissue plasminogen activator (t-PA) inhibitor levels and remarkably also those with high t-PA antigen levels had no lysis. The concentration of t-PA antigen showed a significant increase during heparin infusion, whereas that of PAP and t-PA inhibitor was not influenced. By applying more intensive initial oral anticoagulation, stable therapeutic prothrombin time (PT)-levels were achieved one day earlier and the duration of heparin infusion could be equally reduced compared to the conventional regimen (4.4-5 days vs 5.4-6 days). The activity of coagulation factors II, VII, IX and X had dropped to the same level with both regimens the day heparin was discontinued, observed. The effectiveness of oral anticoagulation after DVT was studied in 596 patients treated for a total of 4450 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1985

Lack of inhibitory effects of alpha 1-acid glycoprotein (orosomucoid) on Plasmodium falciparum invasion of human erythrocytes.

There has been controversy whether the plasma protein, alpha 1-acid glycoprotein (AGP), is able to inhibit invasion of erythrocytes by P. falciparum merozoites. Because AGP resembles a typical cell membrane sialoglycoprotein, it has been proposed that it can inhibit the parasite from interacting with its sialoglycoprotein receptor on the erythrocyte surface. We therefore isolated and tested samples of AGP obtained from a series of separate individuals. For comparative purposes, we also tested AGP prepared from the plasma of patients with elevated levels of AGP, as well as AGP obtained from two commercial sources. The authenticity and purity of the AGP samples was established by SDS-PAGE, radial immunodiffusion, and crossed immunoelectrophoresis. Our results indicated that none of the nine samples tested had any significant inhibitory effects in our P. falciparum invasion assay system.

Electrophoresis, Polyacrylamide Gel↗
PubMed1984

Intensive initial oral anticoagulation and shorter heparin treatment in deep vein thrombosis.

In order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation ("low-dose") and heparin or a more intense oral anticoagulation ("high-dose") with a shorter period of heparin treatment. In the first part of the study 129 patients were randomized. The "low-dose" group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the "high-dose" group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis. In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 ("low-dose") and 3.7 ("high-dose") days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred. Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

Administration, Oral↗
PubMed1984

Local venous infusion of streptokinase in DVT.

Fourteen patients with acute deep vein thrombosis (DVT) of the thigh were treated with different doses of streptokinase (SK) as a local venous infusion. Only the lowest SK-dose given, 4,000 U/h for 72 h, had any effect. Three out of 9 patients on this dose showed significant lysis. However, systemic hemorrhagic side effects occurred in 3 patients, local dermatitis in another 3. The reason for the limited thrombolytic effect and systemic side effects could be that the catheter is not in the immediate vicinity of the thrombus, and that the SK-infusion by-passes the occluded vein segments through collaterals. There is probably no advantage of local venous SK-infusion over systemic SK-therapy in DVT.

Drug Eruptions↗
PubMed1984

A comparative randomized trial of low-dose versus high-dose streptokinase in deep vein thrombosis of the thigh.

Fibrinolytic treatment of acute deep vein thrombosis (DVT) of the leg with high-dose streptokinase (SK) (100,000 U/h) in 39 cases, or low-dose SK (approx 10,000 U/h) in combination with low-dose heparin in 41 cases, was studied in a prospective randomized trial. The degree of thrombolysis was similar in both groups and did not correlate with age or size of the thrombus or with fibrinogen level. The degree of late recanalization was also similar in both groups. There were however significantly more patients with postthrombotic changes in the low-dose group than in the high-dose group after a mean follow-up time of 31 and 38 months respectively. In the low-dose group 2 intracranial hemorrhages occurred (one was fatal) and one patient died of pulmonary embolism, but there were significantly less allergic side effects to SK. There were no cases of such serious side effects in the highdose group. Although low-dose SK has equal thrombolytic effect it seems inferior to high-dose SK, since it probably causes more severe hemorrhagic side-effects.

Clinical Trials as Topic↗
PubMed1984

Caval catheterization in the intensive care nursery: a useful means for providing parenteral nutrition to the extremely low birth-weight infant.

We provided parenteral nutrition to 40 very low birth-weight premature infants (birth weight 815 +/- 17 grams, gestational age 27 +/- 2 weeks) with a superior vena cava catheter. To avoid the risk of transport, catheterization was performed under sterile conditions in the intensive care nursery. The central venous catheter facilitated administration of calories to sustain growth, especially in infants whose catheters remained in place for 3 weeks or longer. The overall incidence of catheter related sepsis was high (30%) but the majority of cases were due to Staphylococcus epidermidis and resolved without incident. Other complications of parenteral nutrition were minimal. This approach is a safe and effective means of providing nutrition to the very low birth-weight infant.

Candidiasis↗
PubMed1984

Hepatitis, epidemiology and liver function in hemophiliacs in Sweden.

The epidemiology of viral hepatitis and liver function were studied in a retrospective survey of 69 patients with moderate and severe hemophilia A and B, and with severe von Willebrand's disease. Forty-nine patients were on prophylactic self-therapy and 20 on episodic treatment by medical personnel. Serologic markers of viral hepatitis (HBsAg, anti-HBs, anti-HBc, anti-HAV, and in some cases HBeAg and anti-HBe) and liver function tests (ASAT, ALAT, IgG) were followed for up to 12 years. There was a history of clinical hepatitis in 19%, and 96% showed some serologic evidence of exposure to hepatitis B virus. Only one patient was a HBsAg carrier. The prevalence of elevated ASAT and/or ALAT was 65% and the incidence 96%. In 68% of the patients there had been a transaminase elevation for more than 6 months. The clinical picture, serologic markers or liver function tests showed no significant difference between the types of hemophilia, amounts and modes of therapy, or age groups. The chronic hepatitis seen in our hemophiliacs seemed to be a slowly or non-progressive disease.

Adolescent↗
PubMed1984

Effects of neoglycoproteins on penetration of Plasmodium falciparum merozoites into erythrocytes in vitro.

Sugars conjugated to bovine serum albumin (neoglycoproteins) were tested for their ability to inhibit Plasmodium falciparum merozoite invasion of red blood cells in an in vitro inhibition assay. The inhibitory effects of the neoglycoproteins on merozoite invasion of erythrocytes were determined by assessing 3H-hypoxanthine incorporation into the cultures. The only neoglycoprotein that caused significant inhibition N-acetyl-glucosamine-bovine serum albumin. A comparison of the inhibitory effects of N-acetyl-glucosamine and N-acetyl-glucosamine-bovine serum albumin showed that N-acetyl-glucosamine-bovine serum albumin was 84 fold more effective than the free sugar in causing 50% inhibition of 3H-hypoxanthine incorporation.

Acetylglucosamine↗
PubMed1984

Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages.

Previous investigations on the mechanism by which the host mounts an immune response against the human malaria parasite Plasmodium falciparum have not resolved whether cell-mediated responses, in the absence of circulating anti-Plasmodial antibodies, can effect the destruction of the intraerythrocytic parasite. We report that the intraerythrocytic parasite P. falciparum is lethally susceptible to the imposition of oxygen-dependent and oxygen-independent factor(s) released by interferon-gamma-activated, monocyte-derived human macrophages. In addition, trophozoite-schizont stage intraerythrocytic parasites were killed on exposure to small amounts of H2O2 generated in cell-free enzyme assays. Although parasiticidal activity was markedly enhanced by the addition of lactoperoxidase and KI, killing was abrogated by the addition of catalase. The ability of freshly isolated human monocytes, monocyte-derived macrophages (MDM), and lymphokine-activated MDM to kill or inhibit the growth and multiplication of the malaria parasites was assessed. Parasites were killed when exposed to monocytes or lymphokine-activated MDM, but not when exposed to nonactivated macrophages. The capacity to activate MDM for microbicidal activity was abrogated on neutralization of crude lymphokines or recombinant interferon-gamma with a monoclonal antibody prepared against interferon-gamma. The intraerythrocytic parasites surviving the cytotoxicity assay were inhibited in their development and appeared to be degenerating, a characteristic of "crisis" forms. Killing of P. falciparum correlated positively with the magnitude of the oxidative response, as evidenced by the reduction of nitroblue tetrazolium to formazan in the mononuclear phagocytes, and by the detection of secreted H2O2. Of particular interest was the observation that only the later developing stage of the intracellular parasite triggered the respiratory burst in the absence of antibody. A role for oxygen-independent parasiticidal factors was suggested by the finding that lymphokine-activated macrophages from a patient with chronic granulomatous disease were able to partially inhibit the growth of P. falciparum, although oxidative metabolism in these cells was impaired.

Erythrocytes↗
PubMed1983

Assay of erythrocyte components as inhibitors of Plasmodium falciparum merozoite invasion of erythrocytes.

Three red blood cell membrane fractions (Band 3, macromolecules exhibiting I antigenic determinants, and a delipidated glycoprotein fraction) were separated from red blood cell membranes and tested for their ability to inhibit penetration of red blood cells by Plasmodium falciparum merozoites in an in vitro inhibition assay. The delipidated glycoprotein fraction (containing the major sialoglycoproteins and devoid of Band 3) was the only fraction that inhibited merozoite invasion. This fraction showed 73% and 70% inhibition at 1 mg/ml and 500 micrograms/ml, respectively, and slight inhibition below these levels.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1981

Properties of the pH-sensitive site that controls the lambda max of Limulus metarhodopsin.

A pH-sensitive site controls the lambda max of Limulus metarhodopsin. The properties of this site were examined using intracellular recordings of the early receptor potential (ERP) as a pigment assay. ERPs recorded over a range of extracellular pHs indicate that the apparent pK of the site is in the range of 8.3-8.6. Several lines of evidence indicate that the site responds directly to changes in extracellular pH (pHo) rather than to changes in intracellular pH(pHi) that follow as a secondary result of changing pHo : (a) the effect of changing pHo was rapid (less than 60 s); (b) when pHo was raised, the simultaneous rise in pHi, as measured with phenol red, was relatively small; (c) raising pHi by intracellular injection of pH 10 glycine buffer did not affect the site; and (d) the effect of changing pH0 could not be blocked by increasing the intracellular pH buffering capacity. It is concluded that the pH-sensitive site on metarhodopsin is on the extracellular surface of the plasma membrane.

Animals↗