Biomedical subjects

M Lev

Publications and source records attributed to M Lev.

At least 19 recordsLinked to original sources

PubMed2005

Diagnostic criteria for schwannomatosis.

The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself.

Diagnosis, Differential↗

PubMed2001

Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial.

PURPOSE: The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival. MATERIALS AND METHODS: Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according to the Daumas-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed gliomas, one an oligodendroglioma. RESULTS: Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis. CONCLUSION: Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.

Adult↗

PubMed2001

Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells.

Natural killer (NK) cells destroy virus-infected and tumour cells, apparently without the need for previous antigen stimulation. In part, target cells are recognized by their diminished expression of major histocompatibility complex (MHC) class I molecules, which normally interact with inhibitory receptors on the NK cell surface. NK cells also express triggering receptors that are specific for non-MHC ligands; but the nature of the ligands recognized on target cells is undefined. NKp46 is thought to be the main activating receptor for human NK cells. Here we show that a soluble NKp46-immunoglobulin fusion protein binds to both the haemagglutinin of influenza virus and the haemagglutinin-neuraminidase of parainfluenza virus. In a substantial subset of NK cells, recognition by NKp46 is required to lyse cells expressing the corresponding viral glycoproteins. The binding requires the sialylation of NKp46 oligosaccharides, which is consistent with the known sialic binding capacity of the viral glycoproteins. These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein.

Animals↗

PubMed2001

Comparison of diameter and perimeter methods for tumor volume calculation.

PURPOSE: Lesion volume is often used as an end point in clinical trials of oncology therapy. We sought to compare the common method of using orthogonal diameters to estimate lesion volume (the diameter method) with a computer-assisted planimetric technique (the perimeter method). METHODS: Radiologists reviewed 825 magnetic resonance imaging studies from 219 patients with glioblastoma multiforme. Each study had lesion volume independently estimated via the diameter and perimeter methods. Cystic areas were subtracted out or excluded from the outlined lesion. Inter- and intrareader variability was measured by using multiple readings on 48 cases. Where serial studies were available in noncystic cases, a mock response analysis was used. RESULTS: The perimeter method had a reduced interreader and intrareader variability compared with the diameter method (using SD of differences): intrareader, 1.76 mL v 7.38 mL (P < .001); interreader, 2.51 mL v 9.07 mL (P < .001) for perimeter and diameter results, respectively. Of the 121 noncystic cases, 23 had serial data. In six (26.1%) of those 23, a classification difference occurred when the perimeter method was used versus the diameter method. CONCLUSION: Variability of measurements was reduced with the computer-assisted perimeter method compared with the diameter method, which suggests that changes in volume can be detected more accurately with the perimeter method. The differences between these techniques seem large enough to have an impact on grading the response to therapy.

Brain↗

PubMed2001

Recognition of viral hemagglutinins by NKp44 but not by NKp30.

Natural killer (NK) cells destroy virus-infected and tumor cells without prior antigen stimulation. The NK cell cytotoxicity is regulated in large part by the expression of NK cell receptors that are able to bind major histocompatibility complex (MHC) class I glycoproteins. NK cells also express lysis triggering receptors specific for non-MHC ligands, including NKp30, NKp44, NKp46 and CD16. However, the nature of their ligands, recognized on target cells, is undefined. We have recently shown that the NKp46 protein, but not the CD16 protein, recognizes the hemagglutinin (HA) of influenza virus (IV) and the hemagglutinin-neuraminidase (HN) of Sendai virus (SV), and that the recognition of HA from IV requires the sialylation of NKp46 oligosaccharides. We have also demonstrated that binding of NKp46 to HA of IV is required for lysis of cells expressing the corresponding glycoproteins by a substantial subset of NK clones. Here we show that NKp44, but not NKp30, can also recognize the HA of both IV and SV and that the recognition of IV HA requires the sialylation of the NKp44 receptor in a similar way to that of NKp46. SV infection of 721.221 cells expressing MHC class I proteinsresulted in the abrogation of the inhibition by NK clones expressing high levels of NKp44. In addition, the binding of NKp44 to HA improves the ability of some NK clones to lyse IV infected cells.

Antibodies, Viral↗

PubMed1999

Is there a potential role for hyoid bone compression in pathogenesis of carotid artery stenosis?

BACKGROUND: Blood flow turbulence and increased shear stress, particularly at sites of sudden, marked arterial wall changes, are significant hemodynamic parameters in the pathogenesis of atherosclerosis. We present a case in which we found the hyoid bone protruding into the carotid vessels and may have been contributing, in part, to atherosclerotic carotid stenosis. CASE PRESENTATION: An 85-year-old woman presenting with left arm and leg weakness consistent with right hemispheric transient ischemic attack. Magnetic resonance arteriography (MRA) and carotid non-invasive studies revealed a 90% stenosis of the right internal carotid artery. At surgery, the hyoid bone on the right side was projecting into the internal carotid artery, causing indentation. There was associated rotation of the internal and external carotid arteries from their normal position. Right carotid endarterectomy was performed and the lateral one-third of the hyoid bone excised to alleviate the external compression. Postoperative spiral computerized tomography (CT) scan of the carotid vessels demonstrated the extent of hyoid resection as well as rotation of the external and internal carotid arteries. CONCLUSIONS: We suggest the possible contribution of hyoid bone compression to the pathogenesis of atherosclerotic carotid artery stenosis. This report also highlights the diagnostic value of CT angiography in the assessment of carotid artery occlusive disease.

Aged↗

PubMed1999

Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors.

OBJECT: In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema. METHODS: Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water. CONCLUSIONS: Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids.

Antineoplastic Agents, Hormonal↗

PubMed1997

Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature.

The clinical, features, serial electrocardiograms, and autopsy findings of a patient with symptomatic complete AV block, who had received mediastinal radiation therapy 8 1/2 years previously, are presented. The cardiac histopathology disclosed immense fibrosis of the conduction system and of the atria and ventricles. The enormous amount of fibrosis was similar in location and intensity to that observed in our previously reported patient (Cohen et al., Arch Intern Med 1981; 141:676-679) who had undergone mediastinal radiation. We conclude that the severe fibrosis was primarily due to radiation, rather than secondary to atherosclerotic coronary artery disease, which also has been described as a consequence of mediastinal radiotherapy. This patient's serial electrocardiograms disclosed evidence of complete block both in the AV nodal area and infra His system, which correlated well with the histopathology. The characteristic clinical features of patients with symptomatic complete AV block post mediastinal radiation therapy are presented, along with a review of the world literature.

Adult↗

PubMed1996

Inhibition of sphingolipid synthesis down-modulates CD4 expression by peripheral blood T lymphocytes and T lymphoma cells.

Recent studies have demonstrated that L-cycloserine, an inhibitor of sphingolipid biosynthesis, interferes with the life cycle of HIV. Experiments with human T cells and CD4+ T lymphoma cells were performed to examine possible mechanisms. L-CS selectively down-modulated CD4 expression without affecting the expression of CD3 and CD8. L-cycloserine also inhibited T cell mitogen responses without affecting IL-2 production. Membranes prepared from L-CS-treated T lymphoma cells showed changes in lipid composition that correlated with changes in membrane microviscosity. These results suggest that normal expression of CD4 may depend upon sphingolipid biosynthesis in contrast with the other CD determinants measured. Selective inhibition of CD4 by L-cycloserine together with its antiviral effects may offer a novel approach for interfering with HIV cell binding and infectivity.

Antigens, CD↗

PubMed1996

L-cycloserine, an inhibitor of sphingolipid biosynthesis, inhibits HIV-1 cytopathic effects, replication, and infectivity.

Drugs that reduce viral production or prevent viral spread by interference with the host's cellular components are unlikely to induce resistance, in contrast to treatment modalities that interact with the HIV-1 life cycle. Two features make L-cycloserine (L-CS) a candidate drug of this kind: (a) L-CS is a potent inhibitor of the sphingolipid pathway (b) sphingolipids, galactocerebrosides, and sulfatides have been shown, by others, to bind gp120. In a feasibility and efficacy study, we have found that L-CS inhibits HIV-1 replication in a CD4+ lymphoid cell line (CEM) as documented by the reduction of syncytium formation, the number of HIV-1 infected cells, and p24 protein production. This observation may lead to a new strategy for the treatment of HIV-1 infection.

Antimetabolites↗

PubMed1996

Vitamin K status influences brain sulfatide metabolism in young mice and rats.

The established role of vitamin K in nutrition is as a cofactor in the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in a limited number of proteins. Administration of the vitamin K antagonist warfarin has previously been shown to decrease brain sulfatide concentrations and decrease brain galactocerebroside sulfotransferase (GST) activity in young mice. A dietary deficiency of vitamin K has now been shown to decrease (P < 0.01) brain sulfatide concentrations of 30-d-old mice significantly (by 21%). Male 21-d-old rats fed an excess of vitamin K for 7 or 14 d had 26 and 31% (P < 0.05) greater GST activity and 15 and 18% (P < 0.05) greater brain sulfatide concentrations, respectively, than controls fed a vitamin K-deficient diet. Male 21-d-old rats fed a diet containing 500 mg of phylloquinone/kg diet had an intermediate response and were vitamin K sufficient by normal criteria. The vitamin K response was observed when either phylloquinone or menaquinone-4 was fed as a source of the vitamin. These data suggest that in addition to its recognized role in Gla synthesis, vitamin K status is important in the maintenance of normal complex lipid sulfatide metabolism in young rats and mice.

Aging↗

PubMed1995

A neutral galactocerebroside sulfate sulfatidase from mouse brain.

We have described an enzyme in brain that catabolizes galactocerebroside sulfatide with a pH optimum of 7.2. To our knowledge, this is the first description of a catabolic enzyme for sulfatide at a neutral pH. Activity at a neutral pH implies a non-lysosomal location for this sulfatidase. Galactocerebroside sulfate sulfatidase (n-sulfatidase) activity was not apparent in crude microsomal extracts and was detected following partial purification of the enzyme. This enzyme, n-sulfatidase, differs from other arylsulfatases in its M(r), inability to bind to concanavalin A, and substrate specificity; n-sulfatidase was unable to hydrolyze p-nitrocatechol sulfate or estrone sulfate. The molecular mass of n-sulfatidase obtained by Sephacryl S-200 chromatography was 72 kDa, and the active fraction from this procedure was purified > 600-fold by isoelectric focusing. Following SDS-polyacrylamide gel electrophoresis, two bands were obtained with apparent molecular masses of 58 and 66 kDa. Enzyme activity was regenerated from both of these bands, with the 66-kDa band showing greater activity. The Km of the sulfatidase was determined as 5.8 x 10(-5) M. The pI of n-sulfatidase was 7.7 in contrast to the pI of 4.9 for the sulfotransferase. No requirement was found for Mg2+ or ATP for sulfatidase activity; vitamin K1 enhanced sulfatidase activity approximately 3.3-fold. Therefore, this enzyme may have a role in the pathogenesis of metachromatic leukodystrophy in which sulfatides accumulate in the nervous and other tissues and in myelination since sulfatides are an important component of myelin.

Animals↗

PubMed1995

Microwave ablation of the atrioventricular junction in open-chest dogs.

The use of microwave energy for ablation of the atrioventricular (AV) junction was examined in open-chest dogs. Using a specially designed microwave catheter and a 2450 MHz generator, microwave energy was delivered to the AV junction according to one of two protocols. In protocol 1, increasing amounts of energy were delivered until irreversible AV block occurred. In protocol 2, only two applications of energy were used, one at low energy and the other at an energy found to be high enough to cause irreversible AV block. Each dog received between one and six applications of microwave energy. The amount of energy delivered per application ranged from 25.6 to 311.4 J. No AV block was seen at 59.4 +/- 28.3 J. Reversible AV block was seen with an energy of 120.6 +/- 58 J. Irreversible AV block was seen at 188.1 +/- 75.9 J. Irreversible AV block could be achieved in each animal. There was no difference in the energy required to cause irreversible AV block between the two protocols. The tissue temperature measured near the tip of the microwave catheter was correlated with both the amount of energy delivered and the extent of AV block caused. Histologic examination demonstrated coagulation necrosis of the conduction system. Microwave energy is a feasible alternative energy source for myocardial ablation. Since tissue damage is due exclusively to heating and the resulting rise in temperature can be measured, microwave energy may have advantages over currently existing energy sources in terms of both titrating delivered energy and monitoring the extent of tissue destruction.

Animals↗

PubMed1995

Cardiac conduction system involvement in sudden death of obese young people.

Involvement of the conduction system in the sudden death of obese young people has not been documented in the literature. We therefore studied the conduction system by serial section examination in 7 subjects, 5 obese and 2 mild to moderately obese, who died suddenly at ages 6, 11, 14, 16, 20, 30, and 32 years of age (5 males, 4 black and 1 white; two females, 1 black and 1 white). Three had a history of sleep apnea. The heart was hypertrophied and enlarged in 6; all 6 had a distinct ventricular septal bulge and epicardial coronary arteries were normal. All had focal mononuclear cells in and around the sinoatrial node and/or its approaches, with marked fat throughout the conduction system in 3, fibrosis of the atrioventricular (AV) bundle and/or the left bundle branch in 5, and the branching bundle sandwiched between the bulbar muscle and the summit of the ventricular septum in 5 (2 with left-sided bundle, 1 with loop formation, and 1 with a markedly fragmented bundle). The AV node was partly within the central fibrous body and/or the atrial septum in 6 patients; focal mononuclear cells were present to a varying degree, with focal fibrosis of the ventricular septum in 6 patients, arteriolosclerosis in 4, and myocardial disarray in 3. The mild to moderately obese patients demonstrated lesser amounts of fat with more fibrosis when compared with the markedly obese. In summary, there are significant pathologic findings in the conduction system in the sudden death of obese young people.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Hypoplasia of the eustachian valve and abnormal orientation of the limbus of the foramen ovale in hypoplastic left heart syndrome.

We examined the eustachian valve and the limbus of the foramen ovale in 42 hearts with hypoplastic left heart syndrome (HLHS) and in 16 normal hearts. In HLHS, only 4.8% of the eustachian valves were moderately to well developed, whereas the remaining 95.2% were abnormal (p < 0.001): 92.9% of the eustachian valves were absent or markedly hypoplastic, and 2.4% had an abnormally redundant and enlarged eustachian valve. The eustachian valve was well developed in 87.5% of normal hearts. In addition, the lesser development of the eustachian valve seemed to correlate with lesser development of the left side of the heart. The limbus was well developed in 100% of the normal hearts and moderately to well developed in only 33.3% of the HLHS group (p < 0.001). Most hearts in the HLHS group had marked hypoplasia of the limbus, which was rotated and deviated so as to be close to the superior vena caval entrance.

Aortic Valve↗

PubMed1994

Conduction system findings in sudden death in young adults with a history of bronchial asthma.

OBJECTIVES: This study was conducted to determine whether there are any pathologic changes in the conduction system when death occurs suddenly in young adults with a history of bronchial asthma. BACKGROUND: There is a worldwide increase in sudden death, especially in young adults with a history of bronchial asthma. METHODS: We studied the conduction system by serial section examination in six male patients (16 to 23 years old) with a history of bronchial asthma who died suddenly. RESULTS: The sinoatrial node artery was narrowed in two patients, with chronic inflammatory cells in three; it was fibrosed in one. The atrioventricular (AV) node was within the central fibrous body in three patients and isolated by fat in one. The AV bundle was markedly fragmented in five patients and fibrosed in two. The right and left bundle branches showed fat, fibrosis and disruption in five patients. Increased fibrosis on the summit of the ventricular septum with patchy fibrosis was present in five patients, and inflammatory cells in the conduction system were found in one. CONCLUSIONS: 1) There are distinct pathologic findings in the conduction system of young adults with a history of bronchial asthma who die suddenly. 2) The significant findings appear to be a markedly fragmented bundle and changes in the sinoatrial node that are not found in normal healthy young adults. 3) The changes in the conduction system may create an arrhythmic event, and sudden death may occur in some persons during an altered physiologic state. 4) We hypothesize that bronchial asthma may be associated with an alteration in immune complexes that affects the conduction system in some patients.

Adolescent↗

PubMed1994

Pulmonary valve eccentricity in d-transposition of the great arteries and implications for the arterial switch operation.

Neoaortic valve regurgitation is a known complication of the arterial switch operation for d-transposition. Its etiology and long-term effects are undetermined. Observations of pathologic specimens from 67 patients with d-transposition of the great arteries with or without ventricular septal defects demonstrated that the pulmonary valve leaflets had unequal cusp sizes leading to eccentric closure. The posterior cusp was usually the largest and was anatomically related to the membranous ventricular septum and the anterior leaflet of the mitral valve. The right cusp was usually the smallest. Differences in cusp sizes were unrelated to age at death, sex or presence of a ventricular septal defect. To determine if eccentricity could be clinically detected, the pulmonary valves in 24 sequential patients with d-transposition were studied echocardiographically and angiographically. Aortic valves were studied for comparison. All pulmonary valves demonstrated eccentric closure in the long-axis echo plane, posterior in 15 patients and anterior in 9. Only 1 aortic valve showed eccentricity. Angiographic findings correlated with echo findings. Sixteen patients underwent arterial switch operations; 3 died. Twelve had angiography at 1 year. Eleven had neoaortic valve regurgitation: 5 grade I, 4 grade II and 2 grade III.

Adolescent↗

PubMed1994

An enrichment object that reduces aggressiveness and mortality in caged laying hens.

The effect on aggressive pecking activity and mortality by an environmental enrichment device was examined. In this study, 2955 White Leghorn chickens from three different lines were used in six separate experiments. Experiments were conducted with chickens during their first or second laying period. Half the cages in each experiment were equipped with colored key rings or an enrichment object manufactured by Gallus Ltd. (Israel). Experimental and control groups of cages were distributed in an alternate serial order for each experiment which lasted for 3, 4, 5, 8, 9, and 10 months. The enrichment devices significantly reduced aggressive head-pecking behavior and significantly decreased the mortality rate from 1.06% per month among the controls to 0.57% among the experimental groups.

Aggression↗