Search PubMed⌕ Search

Biomedical subjects

M Levin

Publications and source records attributed to M Levin.

At least 235 records · Page 13Linked to original sources

Inhibitory and facilitatory effects from the peroneal nerve onto the soleus H-reflex in normal and spinal man.

The effects of conditioning stimulation of a mixed nerve in the leg, the common peroneal nerve (CPN), on the ipsilateral soleus H-reflex were compared with the effects of stimulating its cutaneous branch, the superficial peroneal nerve (SPN), in two groups of subjects--normals and patients with spinal spasticity subsequent to a clinically complete transection of the spinal cord. Condition-test delays of 20 msec to 2 sec, measured from the end of the 20 msec train (3 pulses at 100 Hz), were investigated. In normal subjects, CPN stimulation at 1.4 X MT profoundly depressed the soleus H-reflex. There was an initial depression (peak 40-90 msec) followed by a slow recovery which was incomplete at condition-test delays of 2 sec. One-half of the subjects showed a late facilitation, or disinhibition, peaking at 170-190 msec. The inhibitory effects were attributed to activation of low threshold, groups I and II, muscle afferents because stimulation of the SPN, at 1.5 X threshold for a compound action potential recorded from the CPN, had only facilitatory effects on the soleus H-reflex. Facilitation occurred at condition-test delays of 30-190 msec. The cutaneous stimulation was presumed to activate the largest, A beta, cutaneous afferents as it elicited a weak paraesthesia on the dorsum of the foot. The results suggested that cutaneous afferents may have contributed to the late facilitation seen with CPN conditioning stimulation. In spinal cord-lesioned subjects, CPN stimulation depressed the soleus H-reflex but the decrease was less and the recovery was faster and more complete than in normals. The magnitude of the initial depression at 20-100 msec varied with the severity of the spasticity, subjects with mild spasticity showing less of a depression. Weak cutaneous conditioning stimulation either had no effect or produced a slight depression of the soleus H-reflex, providing clear evidence that transmission in the pathways mediating the facilitatory effects of cutaneous afferents onto extensor motoneuronal pools is depressed in spinal spasticity. This may shift the balance of activity toward the flexor motoneurones, thus favouring the development of, for example, flexor spasms and flexor hypertonia. Since inhibitory effects from cutaneous stimulation are associated with activation of higher threshold afferents in normal man, the present results may reflect a decrease in the threshold for flexor withdrawal reflexes commonly associated with spasticity of spinal origin.

Adolescent↗

Peroxidatic catecholestrogen production by human breast cancer tissue in vitro.

The ability of breast cancer tissues from postmenopausal women to form catechol estrogens was examined by using a product isolation assay. Initial assays were carried out in the presence of either: (a) NADPH, the co-factor for monooxygenase mediated catecholestrogen (CE) formation or; (b) light-activated Tween 80 (LAT-80), a putative organic hydroperoxide co-factor for peroxidatic activity. Under monooxygenase conditions, CE formation by homogenates of 10 tumors did not exceed that obtained with heat denatured tissue. In contrast, 17 of 20 tumors incubated with LAT-80 synthesized significant amounts of CE (8.5 +/- 1.17 2-hydroxyestradiol [2-OH-E2] and 12.8 +/- 2.4 nmol/g protein/10 min 4-hydroxyestradiol [4-OH-E2]). Substitution of cumene hydroperoxide, an organic hydroperoxide, for LAT-80 enhanced estrogen 2/4 hydroxylase (E-2/4-H) activity over 200-fold, making it possible to characterize systematically the peroxidatic activity. The properties of peroxidatic E-2/4-H activity were similar to those of soluble peroxidases isolated from brain, including an acidic pH optimum, localization in the soluble fraction, an apparent Km in the range of 80 microM and an apparent Vmax in the range of 4000 nmol/g/protein/10 min for both 2- and 4-OH-E2. Under optimal assay conditions, peroxidatic E-2/4-H activity was identified in 10 of 13 tumors (2480 +/- 580 nmol/g protein/10 min for 2-OH-E2 and 2790 +/- 600 for 4-OH-E2). The level of activity detected suggests a biological relevance for CE formation by breast cancer tissue.

Animals↗

Decreased sensitivity to heparin in vitro in steroid-responsive nephrotic syndrome.

The in vitro heparin sensitivity of 18 nephrotic children was compared with that of 10 normal children and 13 children with other renal diseases. The influence of age on the heparin sensitivity of 52 normal subjects (aged 12 to 85 years) was also studied. The heparin sensitivity was calculated from the dose-response curve obtained when increasing amounts of heparin were added to plasma and the kaolin partial thromboplastin time (KPTT) was measured. There was a significantly-reduced heparin sensitivity in nephrotic children compared to the control children and a progressive decline in heparin sensitivity with age. In the nephrotic syndrome heparin-sensitivity correlated with albumin and triglyceride concentrations but not with antithrombin III, platelet factor 4, cholesterol, fibrinogen, heparin cofactor II or histidine-rich glycoprotein. Addition of exogenous albumin did not restore the heparin sensitivity of nephrotic plasma. Four patients with Type II hyperlipidemia had a normal sensitivity to heparin. The decreased sensitivity to heparin thus does not appear to be a consequence of the nephrotic state, and may be a reflection of an underlying disturbance of charged macromolecules in steroid-responsive nephrotic syndrome.

Adolescent↗

Inhibition of lipoprotein lipase by plasma from children with the steroid responsive nephrotic syndrome.

The study was designed to investigate the hyperlipidaemia associated with the steroid responsive nephrotic syndrome in children and in particular to examine the mechanism for the delayed clearance of the circulating triglyceride-rich lipoproteins. The possibility that plasma from patients with steroid responsive nephrotic syndrome may contain an inhibitor of lipoprotein lipase activity was studied by examining the effect of the addition of plasma from patients, on normal postheparin lipoprotein lipase activity. Plasma from children with steroid responsive nephrotic syndrome significantly inhibited lipoprotein lipase activity (p less than 0.001), whereas that from patients with familial hypercholesterolaemia and normal children had no significant effect. The inhibition of lipoprotein lipase activity by plasma from patients with steroid responsive nephrotic syndrome correlated significantly with their increased plasma cholesterol and reduced plasma albumin concentrations (p less than 0.001 and less than 0.02, respectively), but there was no significant correlation with plasma triglyceride concentrations. Thus, the degree of inhibition probably reflected the severity of the condition at the time of study. Neither the cholesterol, albumin nor triglyceride concentrations appeared to directly influence the lipoprotein lipase activity of postheparin plasma.

Adolescent↗

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↗