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Biomedical subjects

B Horowitz

Publications and source records attributed to B Horowitz.

At least 145 records · Page 8Linked to original sources
PubMed1987

The development of virus-free labile blood derivatives--a review.

Human blood plasma derived coagulation factor concentrates carry a substantial risk of virus transmission as traditionally prepared. Intensive investigations during the past 5 years have led to the development of several virus sterilization procedures which can be applied to these concentrates as well as to other labile protein derivatives. This review summarizes detailed information which is now available establishing the virucidal potency of these procedures, particularly with regard to the contaminating viruses of most concern: hepatitis B, non-A, non-B hepatitis and the AIDS virus. Currently utilized virus sterilization procedures have greatly reduced or eliminated the transmission of AIDS virus, HIV. The transmission of non-A, non-B hepatitis virus (NANBHV) has also been greatly reduced by some but not all of these procedures. Additional virus safety data in man will be required to establish whether any of the procedures gives products which are totally safe from NANBHV transmission and to assess their impact on other blood-borne viruses.

Animals↗
PubMed1987

Tri(n-butyl) phosphate/detergent treatment of licensed therapeutic and experimental blood derivatives.

Incubation of an AHF concentrate with 0.3% tri(n-butyl)phosphate (TNBP) and 0.2% sodium cholate was shown to inactivate at least 10,000 infectious doses of lipid-enveloped viruses, including hepatitis B and non-A, non-B viruses and HTLV-III [Prince et al., Lancet i, pp. 706-710, 1986]. The use of TNBP/detergent combinations for virus sterilization was evaluated further to determine its effect on the structure and function of a wide variety of blood proteins. Vesicular stomatitis and Sindbis viruses were used as markers of virus inactivation. TNBP/detergent treatment did not significantly alter the function of AHF, factor VII, factor IX, factor X, fibrinogen, factor XIII, fibronectin, anti-HBsAg and anti-HA in normal serum globulin, haptoglobin, tumor necrosis factor, alpha-interferon, and both native and chemically polymerized stroma-free hemoglobin. As compared with partially purified derivatives, the extent of virus sterilization of plasma and component cryoprecipitate with 0.3% TNBP and 0.2% sodium cholate at ambient temperature could be improved by raising the TNBP concentration and temperature. Virus sterilization by TNBP/detergent mixtures appears to be generally applicable to blood protein derivatives.

Antiviral Agents↗
PubMed1987

Laboratory and preclinical evaluation of the virus safety of coagulation factor concentrates.

Studies of virus sterilization of coagulation factor concentrates using marker viruses, AIDS, hepatitis B (HBV) and non-A, non-B hepatitis (NANBHV) viruses indicate the following: Strategies adopted to stabilize coagulation factors to heat denaturation, including addition of high concentrations of solutes or lyophilization, stabilize virus. At 60 degrees C, heating in the liquid state provides more rapid virus kill than heating in the lyophilized state with 2% residual moisture. To achieve the same virucidal potency as achieved on heating albumin at 60 degrees C for 10 hours, stabilized coagulation factor concentrates would require a substantial increase in the dose of heat. The rate of inactivation by either thermal or solvent/detergent methods slows with time. Improved virus kill is attained more easily by increasing the temperature than by extending the duration of exposure. Viruses vary widely in their sensitivity to thermal denaturation or solvent/detergent action. Because studies on the rate of inactivation of HBV and NANBHV are not feasible, assessment of their sensitivity is at best approximate. Sensitivity to thermal inactivation appears to follow the order HTLV-III greater than VSV, EMC greater than NANBHV?, Sindbis much greater than HBV. Sensitivity to organic solvent/detergent mixtures appears to follow the order HTLV-III greater than Sindbis, Sendai, HBV?, NANBHV? greater than VSV much much greater than EMC. Protein enveloped forms of NANBHV must occur rarely or not at all. Use of marker viruses to compare virucidal potency of methods that inactivate by different mechanisms may lead to erroneous conclusions; however, marker virus data probably provide useful comparisons of related sterilization methods or of a single method applied to different protein mixtures. If virus sterilization processes are to be validated in a manner which enables a meaningful comparison between laboratory and clinical results, higher titers of virus will be required.

Blood Coagulation Factors↗
PubMed1986

Sterilisation of hepatitis and HTLV-III viruses by exposure to tri(n-butyl)phosphate and sodium cholate.

Blood product sterilisation with 0.3% tri(n-butyl)phosphate (TNBP)/0.2% sodium cholate (CA), a combination known to permit high recovery of factor VIII and factor IX, was evaluated for its effect on hepatitis B (HBV), non-A, non-B (NANB), and human T-lymphotropic type III (HTLV-III) viruses. 2 chimpanzees received factor VIII preparations contaminated with 10(4) chimpanzee infectious doses (CID50) of HBV and treated with TNBP/CA; neither had evidence of HBV infection during 9 months follow-up, but hepatitis B surface antigen (HBsAg) developed 5 and 6 weeks, respectively, after challenge with untreated inoculum. 2 chimpanzees were similarly exposed to 10(4) CID50 of Hutchinson NANB inoculum treated with TNBP/CA; neither became infected during 26 weeks of follow-up but both had characteristic NANB-associated ultrastructural changes 3-5 weeks after exposure to untreated inoculum. 2 chimpanzees inoculated with 80 ml of TNBP/CA-treated factor VIII derived from a pool of thirteen lots obtained from five US manufacturers remained free of any evidence of NANB infection during 32 weeks of follow-up. Subsequently, NANB infection developed in both animals 3-4 weeks after exposure to untreated inoculum. Exposure of HTLV-III diluted into a factor VIII preparation to TNBP/CA inactivated greater than or equal to 10(4.2) tissue culture infective doses within 20 min at 24 degrees C.

Animals↗
PubMed1986

Intrathecal interferon in subacute sclerosing panencephalitis.

Five patients with clinically advanced subacute sclerosing panencephalitis (SSPE) were given human leukocyte interferon (IFN) by the lumbar route, 1 million IU every other day for a total of 30 days. Intrathecal IFN produced a meningeal inflammatory reaction in all patients and was associated with transient hemiparesis in 1. It persisted in the cerebrospinal fluid at measurable levels for 48 hours after a single injection. Although improvement was temporally related to intrathecal IFN in 1 patient, it is not clear whether this was induced by IFN or a spontaneous remission. A randomized controlled trial would be necessary to evaluate IFN critically as a therapy for SSPE.

Adolescent↗
PubMed1986

Initial combination therapy with YAG laser photoresection and irradiation for inoperable non-small cell carcinoma of the lung. A preliminary report.

Patients presenting with inoperable non-small cell carcinoma of the lung and major symptomatic bronchial obstruction were treated initially with debulking of the airways by YAG laser, followed by conventional external-beam radiotherapy. The former method was used to minimize postobstructive pneumonitis or respiratory failure (or both) that often complicates major brochial obstruction and also to lessen the burden of tumor to be treated by radiotherapy. The preliminary results of 19 patients treated in this manner are reported, emphasizing the impact of this combined method on morbidity and mortality.

Adenocarcinoma↗
PubMed1985

Formation of delta tra F' plasmids: specific recombination at oriT.

Delta tra F' plasmids can be isolated from matings between Hfr donors and recA- recipients, with selection for transfer of proximal chromosomal genes. Previous experiments indicate that F DNA from the neighborhood of the transfer origin up to the proximal junction with the chromosomal DNA is present on these plasmids, together with chromosomal segments, some of which belong to distinct size classes. We have sequenced across the novel joints contained in five delta tra FproA+ plasmids and in five delta tra FpurE+ plasmids, and we have compared these with the F sequence near oriT and with a chromosomal site near purE. The previously reported specificity in formation of some of these classes is confirmed at the nucleotide sequence level. The F DNA in nine of these novel joints extended beyond the nicking sites identified by others in lambda oriT+ bacteriophages up to a position between two sequenced oriT- mutations. Small plasmids containing these novel joints are mobilized in trans by pOX38 at frequencies less than 5 X 10(-7) times the mobilization frequencies for similar plasmids that contain oriT. The relations of these findings to the location of the nicking site at oriT are discussed.

Bacteriophages↗
PubMed1985

Fibronectin and fibrin gel structure.

Plasma fibronectin is covalently incorporated into alpha-chains of fibrin gels in the presence of Factor XIII activated by thrombin (FXIIIaT) but not by Factor XIII activated by the snake venom enzyme batroxobin (FXIIIaB). FXIIIaB catalyzes introduction of gamma-gamma cross-links in fibrin but cross-linked alpha-chains are not formed. In the presence of FXIIIaT, fibrin gels formed by batroxobin incorporated fibronectin and the alpha-chains are cross-linked indicating that FXIIIaB has a different substrate specificity from FXIIIaT. In the presence of FXIIIaT the incorporation of fibronectin approaches 1 mol/340 kDa unit weight of fibrin. Fibronectin when present in a fibrinogen thrombin mixture containing FXIII does not influence the clotting time of the system nor the release of fibrinopeptides. Incorporation of fibronectin is not appreciable before the gel point. This indicates that the polymerization and gelation of fibrinogen is essentially not perturbed by the presence of fibronectin and that fibrin in the gel matrix rather than the fibrin polymers formed prior to gel point is the preferred structure for fibronectin incorporation. Incorporation of fibronectin into fibrin gels during formation leads to an increase in turbidity and a small decrease in Ks (permeability coefficient). This suggests that the width of the strands in the gel increases as a result of fibronectin incorporation. Fibronectin is also incorporated into preformed gels having completely cross-linked gamma- and alpha-chains perhaps indicating that the sites in fibrin involved in fibronectin incorporation are different from those involved in fibrin cross-linking. FXIIIaT appeared to be adsorbed to fibrin gel matrix in the presence but not in the absence of calcium ions.

Batroxobin↗
PubMed1985

The effect of carbonic anhydrase inhibition on breathing movements and electrocortical activity in fetal sheep.

Fetal breathing movements (FBM) indicated by repetitive negative intrathoracic pressures and biparietal electrocorticograms (ECoG) were recorded from 8 fetal sheep for 3 h before (control) and 3 h after the administration of a carbonic anhydrase inhibitor, acetazolamide. FBM and the low voltage (LV) ECoG state occurred 36 +/- 5% (SEM) and 60 +/- 3% of the control period, respectively. Virtually no FBM occurred during high voltage (HV) ECoG while in 57 +/- 6% of the LV state the fetuses were making FBM. The peak magnitude of the negative intrathoracic (tracheal) pressure deflections was 4 +/- 1 Torr. Following acetazolamide the incidence of FBM rose to 53 +/- 4% (P less than 0.01) but there was no significant change in the incidence of the LV state (58 +/- 3%). Most of the increase in the incidence of FBM remained confined to periods of LV ECoG activity so that an increased proportion of this state (88 +/- 2%, P less than 0.001) was occupied with respiratory efforts. The amplitude of the FBM also increased to 8 +/- 1 Torr (P less than 0.05). The increased incidence and depth of FBM is most likely due to an elevated hydrogen ion concentration and differs from a fetal respiratory acidosis induced by increasing the inspired CO2 fraction to the ewe in that the respiratory stimulation induced by acetazolamide is not associated with an increased incidence of the permissive LV ECoG state.

Acetazolamide↗
PubMed1985

Biochemistry of whole blood in poly(ethylene-co-ethylacrylate) experimental blood containers.

The biochemical status of whole blood stored in containers fabricated of ethylene ethylacrylate (EEA) film was monitored at several times during 4 weeks of storage at 4 degrees C. Fifteen biochemical indicators were studied to reflect on erythrocyte integrity, cellular metabolism, plasma protein stability, and microaggregate formation. Comparison to storage in polyvinyl chloride (PVC) containers was made by distributing aliquots from each unit of blood among the containers being compared. Whole blood in EEA developed significantly higher levels of plasma hemoglobin, erythrocyte osmotic fragility, and D-glycerate-2,3-diphosphate (2,3-DPG), and somewhat greater glucose utilization, lactate production, and pH. These biochemical differences were not of great magnitude and the data suggest that EEA containers are compatible with the storage of whole blood.

Acrylic Resins↗
PubMed1985

Stabilization of red blood cells by the plasticizer, diethylhexylphthalate.

The red blood cells of blood stored in containers made of polyvinylchloride (PVC) film are osmotically more stable and lose on average about 1/3 less hemoglobin than when blood is stored in another plastic [poly-(ethylene-co-ethyl acrylate); EEA]. The stability of uniform volumes of stored red blood cells varies directly with PVC surface area, whereas changes in EEA surface area have comparatively little or no effect. PVC contains high concentrations of the plasticizer, diethylhexylphthalate (DEHP), known to migrate into blood and to have a high potential for toxicity. To determine if DEHP could be the red cell stabilizing agent in PVC, whole blood was stored in containers made from EEA into which was incorporated varying amounts of DEHP. Incorporation of DEHP into EEA significantly reduced erythrocyte osmotic fragility (p = 0.01). The degree of reduced fragility correlated with the level of DEHP in the cell phase implicating DEHP in PVC containers as the stabilizing agent for red cells.

Acrylic Resins↗
PubMed1985

A new assay for fibronectin opsonic activity and its application to plasma and plasma fractions.

A homologous assay system for human plasma fibronectin opsonic activity is presented. The system utilizes peripheral leukocytes purified from leukocyte concentrates and a metabolizable, radiolabeled lipid emulsion which has been gelatin-coated. The uptake of radiolabeled lipid was shown to depend on the presence of fibronectin and was stimulated by the addition of heparin. Both polymorphonuclear leukocytes (PMNs) and monocytes were active in this system. That at least a portion of the incorporated radiolabeled lipid emulsion was phagocytosed was indicated through the use of metabolic inhibitors, trypsin, and direct electron microscopic observation. This assay was applied to the analysis of donor plasma and plasma fractions. Opsonic activity levels measured with this assay system were shown to correlate (p = 0.05) with the level of fibronectin antigen in 17 samples of dialyzed normal donor plasma. Fibronectin opsonic activity was retained by outdated liquid plasma, cryo-depleted plasma, and cryoprecipitate; however, Cohn fraction I appeared to lose considerable fibronectin opsonic activity relative to fibronectin antigen.

Biological Assay↗
PubMed1985

Quantitative assays for evaluation of HTLV-III inactivation procedures: tri(N-butyl)phosphate:sodium cholate and beta-propiolactone.

Human T-lymphotropic retrovirus type III (HTLV-III) can be quantitatively assayed for infectivity by inoculation of serial dilutions into cultures of the H-9 cell line and testing for reverse transcriptase in the culture supernatants. Sequential harvests revealed that 14 days of incubation of cultures fed twice weekly was sufficient to reveal maximal titers. Stocks prepared from unconcentrated H9:HTLV-IIIb supernatants have contained from 10(4.5) to 10(6.0) (TCID50)/ml. Stocks prepared by 100-fold concentration of such fluids by pelleting or by polyethylene glycol precipitation followed by pelleting onto sucrose cushions contained 10(6.0)-10(6.5) TCID50/ml. Preliminary studies are under way to utilize this system for evaluation of sterilization processes which can be applied to blood derivatives. Exposure of HTLV-III suspended in Factor VIII preparations to 0.3% tri(n-butyl)phosphate-0.2% sodium cholate resulted in inactivation of greater than or equal to 10(4.5) TCID50 in 2.5 h at 27 degrees C. Exposure of HTLV-III suspended in 4 g of gamma-globulin per 100 ml to 0.14% beta-propiolactone for 4 h at room temperature at pH 8.0 inactivated greater than or equal to 10(4.5) TCID50. However, exposure to gamma-globulin alone inactivated about 99% of HTLV-III infectivity.

Cell Line↗
PubMed1984

Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether.

Titrated stocks of hepatitis B virus and Hutchinson strain non-A, non-B hepatitis virus were diluted in normal serum to contain, respectively, greater than or equal to 10(6) and greater than or equal to 10(4) chimpanzee infectious doses (CID50) per milliliter and exposed to 1% Tween 80 and 20% ether at 4 degrees C for 18 h. After evaporation of the ether, the treated sera were each inoculated into two chimpanzees. The animals remained free of serologic and biochemical evidence of hepatitis during a 6-month follow-up period, and were then shown to be susceptible to infection by challenge with the original untreated inocula. To assess the effect of exposure to Tween 80/ether on coagulation factors, four lots of antihemophilic factor (AHF) concentrate and 2 lots of commercial factor IX concentrate were treated as above. For the AHF concentrate there was an average of 70% recovery of factor VIII procoagulant activity, 93% recovery of factor VIII-related antigen, and 73% recovery of fibronectin opsonin activity and no detectable change in ristocetin cofactor activity or in fibronectin antigen. Crossed immunoelectrophoresis revealed no change in migration rate of fibrinogen, fibronectin, and von Willebrand factor (vWF), although the quantity of fibrinogen was reduced. Factor VIII procoagulant activity and vWF activity remained associated during chromatography on BioGel A15.

Animals↗
PubMed1983

Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors.

A total of 49 patients were treated using intraarterial cis-platinum infusions at a dose of 100 mg/m2. The patients were separated into three groups. There were 13 patients with metastatic tumors, 10 with recurrent malignant gliomas, and 22 patients with high-grade gliomas who received intraarterial cis-platinum as part of an adjuvant program. In addition, four nongliomatous primary brain tumors were treated in this fashion. Cis-platinum was filtered immediately prior to intraarterial infusion using a 0.22-micron filter. Response to treatment was evaluated by follow-up CAT scans and neurologic examinations. There were three complete and eight partial responses in metastatic tumors, and eight partial responses in recurrent gliomas. The median survival was 19 weeks for patients with metastatic disease, and 16 weeks for patients with recurrent gliomas. Those high-grade glioma patients who received intraarterial cis-platinum as adjuvant chemotherapy along with CCNU and radiation therapy had a projected median survival of 91+ weeks. Toxicity from intraarterial cis-platinum following drug filtration was markedly reduced when compared with previous reports. Only five patients experiencing visual or central nervous system toxicity utilizing filtered cis-platinum and no radiographic or histopathologic evidence of central nervous system toxicity was observed. Bilateral deafness was observed following vertebral artery infusion in both patients treated in this manner and thus vertebral artery infusions should be avoided. Systemic toxicity was mild. Intracarotid infusion is a safe, well-tolerated delivery system for filtered cis-platinum with a high response rate for patients with both metastatic and primary malignant brain tumors.

Brain↗