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Biomedical subjects

M Levin

Publications and source records attributed to M Levin.

At least 73 records · Page 4Linked to original sources

Platelet immune complex interaction in the pathogenesis of Kawasaki disease.

We have shown that the thrombocytosis which occurs in the 3rd and 4th week of Kawasaki disease is associated with the appearance in the circulation of platelet aggregating factors detected by the PAT test. These factors induce aggregation and serotonin release from normal platelets. The aggregation can be blocked by EDTA and Prostacyclin. The aggregating factor appears to be of high molecular weight, and its activity was lost following fractionation at low pH. The platelet aggregating activity was significantly associated with the presence of IgG immune complexes, and these features suggest that IgG immune complexes are responsible for the platelet aggregating activity.

Antigen-Antibody Complex

Platelet-derived growth factors as possible mediators of vascular proliferation in the sporadic haemolytic uraemic syndrome.

Mitogenic activity was measured in matched plasma and serum samples from 17 children with typical epidemic haemolytic uraemic syndrome (HUS), 13 with atypical sporadic HUS, 7 with other renal diseases, and 8 normal children. The serum mitogenic activity of the normal children (median 18.35, range 15-35 U/ml) greatly exceeded that of plasma (median 5.4, range 1.04-11.9 U/ml). Patients with atypical sporadic HUS had raised plasma mitogenic activity (median 9.35, range 0-35 U/ml, p less than 0.01). Both plasma and serum from children with the typical epidemic form of HUS had low or undetectable mitogenic activity (median for plasma 1.0, range 0-5.9 U/ml, p less than 0.001; median for serum 1.85, range 0-23.8 U/ml, p less than 0.005). These low concentrations in typical epidemic HUS were associated with the presence of an inhibitor of cell growth. The results suggest that there is intravascular release of platelet mitogens in atypical sporadic HUS and that these mitogens may therefore be mediators of the vascular proliferative lesions.

Adolescent

A simple method for cryopreservation of human sperm.

A simple method of cryopreservation of human sperm is discussed. Fifteen randomly collected samples were frozen and assessed after storage in liquid nitrogen. The mean recovery rate was 77% (range 62-91%) with no significant deterioration after 4 weeks' storage. The cryopreserved sperm is used in an artificial insemination by donor clinic and also sent to distant centres in the RSA and neighbouring countries. The method is also used for the cryopreservation of specimens of the sperm of patients undergoing vasectomy or radiotherapy, and in the Groote Schuur Hospital in vitro fertilization programme. Modification of the method will also allow human embryos to be frozen.

Freezing

Prostacyclin deficiency in a young woman with recurrent thrombosis.

A young woman with recurrent deep venous thromboses and spontaneous abortions was studied. She suffered an ovarian infarction followed by aortic thrombosis and renal failure. Evidence for deficient prostacyclin production was found and she responded to treatment with a prostacyclin infusion. This syndrome is identical with that seen in women with the lupus anticoagulant, but the lupus anticoagulant was not detected and no other cause was identified.

Abortion, Habitual

Expression of aldolase A messenger RNAs in human adult and foetal tissues and in hepatoma.

3 specific cDNA clones for human aldolase A were isolated from a human muscle library. One of them was subcloned in M 13 phage, then used as a probe to investigate the patterns and the levels of aldolase A mRNA in various human tissues. Two mRNA species differing in length were observed. The lighter one -1550 bases- was found specific to skeletal muscle; its amount increased during muscle development. The heavier aldolase A mRNA -1650 bases- accounted for foetal and ubiquitous presence of aldolase A isozyme. The resurgence of aldolase A in hepatomas occurred through this latter mRNA species.

Animals

Pulmonary thromboembolism in children.

Pulmonary embolism in childhood is a rare but under-diagnosed condition. We report four children aged 5 to 13 years presenting with pulmonary emboli, their primary diagnoses being craniopharyngioma, asthma, Crohn's Disease and Reye's syndrome. The diagnosis was supported by technetium micro aggregate lung perfusion scans in three of the children and in the fourth, the only child to die, by autopsy. Three of the children had markedly elevated plasma osmolalities, one as a result of his diabetes insipidus and two following hyperosmolar treatment for cerebral oedema. The child who died was found to have a femoral vein thrombosis but the sites of origin of emboli in the other children were not defined.

Adolescent

Effect of dispersion of vessel diameters and lengths in stochastic networks. I. Modeling of microcirculatory flow.

A microvascular network model is proposed with random arrangement and random dimensions of vessels. In addition to stochasticity of the topological characteristics of the model networks, as previously introduced by Fenton and Zweifach (1981, Ann. Biomed. Eng., 9, 303-321), the vessel diameters and lengths are treated as random variables following certain probability distributions for each vascular order. Flow and pressure distributions are calculated for each network configuration assuming a linear relationship between the blood flow rate and pressure drop for each vascular segment. The mean, coefficient of variation, skewness, kurtosis, and histograms of the hemodynamic variables are computed using an ensemble of random networks. The results indicate that dispersion of vessel diameters and lengths may significantly affect the distributions of microvascular variables such as capillary flow and pressure, and the flow distribution at bifurcations. It is shown that the dispersion of vessel diameters causes a decrease of total flow whereas the dispersion of lengths causes its increase.

Animals

Effect of dispersion of vessel diameters and lengths in stochastic networks. II. Modeling of microvascular hematocrit distribution.

A microvascular network model described in the preceding paper (B. Dawant, M. Levin, and A. S. Popel, 1986, Microvasc. Res. 31, 203-222) featuring random distribution of vessel diameters and lengths, is extended to calculate the distributions of red blood cell flux and discharge hematocrit throughout the network. A relationship between red blood cell fluxes and blood flow rates at vascular bifurcations is incorporated into the model, and the effect of the form of this relationship on RBC distribution is investigated. The mean capillary discharge hematocrit is sensitive to the variation of parameters describing this relationship; thus detailed experimental information is required for bifurcations of different sizes and types.

Analysis of Variance

Complex chromosomal abnormalities in acute nonlymphocytic leukemia.

A comparison of chromosome abnormalities between 31 cases of de novo acute nonlymphocytic leukemia (ANLL) with complex karyotypes and 30 cases of secondary ANLL or dysmyelopoietic syndromes (DMS) revealed significant differences. Hyperdiploidy and partial or complete monosomy 5 were more frequent in complex de novo ANLL, whereas, hypo or pseudodiploidy and partial or complete monosomy of chromosome #7 were more frequent in secondary ANLL/DMS. Monosomy 17 and partial deletion of the short arm of chromosome #12 (12p-) occurred more commonly in de novo ANLL and secondary ANLL/DMS, respectively, but were not statistically significant. Therefore, although the abnormalities found in the two groups were of the same basic type, the frequencies of occurrence differed. These findings suggest the role of as yet unknown agents in the etiology of some so called de novo ANLL, and that different mutagenic or carcinogenic agents may produce different chromosomal abnormalities.

Acute Disease

Specific lysis of varicella zoster virus-infected B lymphoblasts by human T cells.

Epstein-Barr virus-transformed human B cells expressed cell surface varicella-zoster virus (VZV) antigens after superinfection with VZV although they did not form infectious centers in a plaque assay. The VZV-superinfected cells were lysed by autologous VZV-stimulated T-cell lines and their derivative clones. The effector cells were specific for VZV and an HLA DR antigen and were T4+. The specificity of lysis of Epstein-Barr virus-transformed, VZV-superinfected targets by prestimulated mononuclear cells in this system contrasted with the unrestricted lysis seen when the targets were VZV-infected fibroblasts.

Antigens, Viral

Multiple tracer dilution estimates of D- and 2-deoxy-D-glucose uptake by the heart.

Permeability-surface area products of the capillary wall, PSc, and the myocyte sarcolemma, PSpc, for D-glucose and 2-deoxy-D-glucose were estimated via the multiple indicator-dilution technique in isolated blood-perfused dog and Tyrode-perfused rabbit hearts. Aortic bolus injections contained 131I-albumin (intravascular reference), two of three glucoses: L-glucose (an extracellular reference solute), D-glucose, and 2-deoxy-D-glucose. Outflow dilution curves were sampled for 1-2.5 min without recirculation. The long duration sampling allowed accurate evaluation of PSpc by fitting the dilution curves with a multiregional axially distributed capillary-interstitial fluid-cell model accounting for the heterogeneity of regional flows (measured using microspheres and total heart sectioning). With average blood flow of 1.3 ml . g-1 . min-1, in the dog hearts the PSc for D-glucose was 0.72 +/- 0.17 ml . g-1 . min-1 (mean +/- SD; n = 11), and PSpc was 0.57 +/- 0.15 ml . g-1 . min-1. In the rabbit hearts with perfusate flow of 2.0 ml . g-1 . min-1 (n = 6), PSc was 1.2 +/- 0.1 and PSpc was 0.4 +/- 0.1 ml . g-1 . min-1. PSc for 2-deoxy-D-glucose was about 4% higher than for D-glucose and L-glucose in both preparations. Relative to L-glucose, there was no measurable transendothelial transport of either dextroglucose, indicating that transcapillary transport was by passive diffusion, presumably via the clefts between cells. The technique allows repeated measurements of D-glucose uptake at intervals of a few minutes; it may therefore be used to assess changes in transport rates occurring over intervals of several minutes.

Animals

Preparation and characterization of a polyvalent human melanoma antigen vaccine.

A polyvalent melanoma tumor antigen vaccine was prepared from antigens shed by a pool of human melanoma cells cultured in serum-free medium. The vaccine contained multiple melanoma associated antigens (MAAs) and was free of detectable fetal calf serum (FCS) proteins and Dr antigens. Three batches of vaccine prepared several months apart contained the same spectrum of tumor antigens. Thirteen patients with metastatic malignant melanomas were immunized intradermally with escalating doses of the vaccine in a Phase I study. There was no toxicity other than transient urticaria at the injection site. Humoral immunity, assayed by indirect immunoprecipitation, was augmented in five (38%) patients. Cellular immunity, assayed by delayed-type cutaneous hypersensitivity, was induced in four (31%) patients. Skin tests to a control vaccine prepared from pooled allogeneic lymphocytes were negative. Cutaneous metastases regressed completely in one patient who is now disease free after 2 years, and multiple cutaneous metastases have remained stable for 14 months in another patient. These results indicate that active immunization to a partially characterized polyvalent melanoma antigen vaccine is safe and can increase immunity to melanoma in some patients.

Adult

Steroid-responsive nephrotic syndrome: a generalised disorder of membrane negative charge.

A simple chemical test, based on the binding of the cationic dye alcian-blue 8GX (AB), has been devised to measure negative charge on cell membranes. The test has demonstrated that AB binding to red blood cells and platelets is significantly less in children with steroid-responsive nephrotic syndrome (SRNS) or nephrotic syndrome associated with focal segmental glomerulosclerosis than in normal controls. However, the sialic acid content of the nephrotic cell membrane is normal. This suggests that a generalised loss of membrane negative charge occurs in SRNS and that this is due to neutralisation rather than absence of anionic groups.

Adolescent

Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis.

The role of platelets in the pathogenesis of vasculitis and the formation of coronary artery aneurysms was studied in 19 children with Kawasaki disease and five with polyarteritis. All patients with Kawasaki disease developed thrombocytosis in the third week of illness. The peak platelet count was significantly correlated (p less than 0.005) with the subsequent development of coronary artery aneurysms. The rise in platelet count was associated with the appearance in the circulation of a factor that induced aggregation and serotonin release in normal platelets. This factor was shown to be of high molecular weight, and its activity was lost at low pH--features suggestive of an immune complex. Immune complexes, detected by precipitation with polyethylene glycol, also appeared in the circulation as the platelet count increased. These complexes induced platelet aggregation, and there was a significant correlation (p less than 0.001) between the concentrations of IgG and IgA in the polyethylene glycol precipitated material and the platelet aggregating activity. Similar platelet aggregating activity was also detected in patients with polyarteritis but followed a different time course, persisting in the circulation for several months in association with continued disease activity. These findings imply that different mechanisms have a role in distinct phases of Kawasaki disease. The initial feverish phase (probably infective) is probably followed by an immune complex vasculitis that occurs when antibodies to the initiating agent appear in the circulation. The immune complexes aggregate platelets and induce release of serotonin. Platelet derived vasoactive mediators may increase vascular permeability and facilitate further deposition of complexes in the tissues.

Aneurysm

Topical acidification promotes healing of experimental deep partial thickness skin burns: a randomized double-blind preliminary study.

The effects of three buffered solutions with pH values of 3.5, 7.42 and 8.5, respectively, on the healing rate of deep partial skin thickness burns, was followed for 21 days in 16 guinea-pigs. Two symmetrical burns were inflicted on the back of each animal and then each individual wound was dressed with an irrigation disc dressing; solutions were coded (no. 1 to no. 3) and the animals were randomly divided and blindly treated as follows: Group A, solution no. 1 v. solution no. 2 (n = 4); Group B, solution no. 2 v. solution no. 3(n = 4); Group C, solution no. 1 v. solution no. 3(n = 4); Group D, non-irrigated disc dressings (n = 4). The solutions were applied to the surface of the burn wounds at a rate of 0.15 ml/cm2. Dressings were changed every 7 days to assess contraction and epithelialization by a sonic digitizer. On post-burn day 21 the newly formed scar tissue was measured in all wounds. After computation of the healing rate at the end of the study, the data were then related to the coded treating agent. Contraction did not differ in all test groups during the study. Epithelialization was significantly faster in the pH 3.5-treated burns than in the other treated wounds (P less than 0.001). The present study indicates that topical acidification of experimental deep partial skin thickness burns promoted healing. The precise mechanism should be elucidated.

Administration, Topical

The salutary effects of the bed on the survival of experimental flaps.

The present study indicates that the distal, random segment of an axial pattern experimental flap can be partially salvaged by employing local pressure, which provides favorable contact with the bed. This portion of the flap could be considered as a composite skin graft. Serial India ink injections demonstrated that its physiological take resembles that of a split-thickness graft, dominantly depending on the blood vessels emerging from its bed, and to a lesser extent on those provided by its proximal segment and adjacent skin edges. Increasing the topical flap humidity hindered, rather than improved, its survival.

Animals

Drug-loaded synthetic dressings: effect on contraction, epithelialization, and collagen synthesis of deep second-degree experimental burns.

The effect of drug-loaded synthetic dressings on the contraction, epithelialization, and collagen synthesis of deep second-degree burns was followed for 21 days in 44 guinea pigs. Two symmetrical burns were inflicted on the back of each animal; the animals were then divided at random into the following test groups: Group 1 (n = 10), a prefabricated, precut, pliable, and noncracking dressing designated as Dimac (DM), versus Dimac plus 2% silver sulfadiazine (DM+); Group 2 (n = 10), Hydron loaded with 2% silver sulfadiazine (HAgS) one versus fine mesh gauze and 1% silver-sulfadiazine cream (GAgS); Group 3 (n = 12), Hydron (Hyd) versus fine mesh gauze (G); Group 4 (n = 4), fine mesh gauze versus Telfa (Tel); Group 5 (n = 6), Telfa versus Telfa; Group 6 (n = 2), gauze versus gauze. Epithelialization and contraction rates were measured at dressing changes on postburn days 6, 12, 18, and 21, with a computerized sonic digitizer. Collagen biosynthesis was measured from the wound scar on PBD 21 and expressed as relative collagen biosynthesis. Contraction on PBDs 18 to 21 was significantly lower (p less than 0.05) in the DM and DM+ treated burns. Epithelialization of the DM and DM+ treated groups on PBD 21 was significantly (p less than 0.05) higher than in the Hyd, HAgS, GAgS, and Tel treated burns, and did not differ from the G treated wounds. The relative collagen biosynthesis method was inapplicable to this burn wound model.

Animals