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Biomedical subjects

M Mandel

Publications and source records attributed to M Mandel.

At least 73 records · Page 4Linked to original sources
PubMed1993

Identification of DNA adducts at specific locations by sequencing techniques.

1. A simple procedure for the accurate identification of the positions of adduct formation when viral M13mp18 single stranded DNA is treated with chloroacetaldehyde (CAA) is presented. 2. The normal dideoxy sequencing reaction protocol was employed except no dideoxy nucleotides were used to cause chain termination. 3. Instead, the CAA adducted bases of the template DNA act as points of polymerase fall off causing the appearance of bands of DNA sequencing gel autoradiographs marking locations where adduct formation may have occurred.

Acetaldehyde↗
PubMed1993

Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

Antibodies, Neoplasm↗
PubMed1993

Multiple copies of a DNA sequence from Pseudomonas syringae pathovar phaseolicola abolish thermoregulation of phaseolotoxin production.

Phaseolotoxin, a phytotoxin of Pseudomonas syringae pv. phaseolicola, is produced at 18 degrees C but not at 28 degrees C. Here we report that a fragment (24.4 kb) cloned from the wild-type strain, which does not harbour a gene(s) involved in phaseolotoxin biosynthesis, abolishes this thermoregulation in the wild type and suppresses a Tox- mutant at both temperatures. A subclone harbouring a 485 bp fragment contains motifs that are characteristic of DNA-binding sites. In mobility shift assays we have detected a protein(s) from the wild-type and the mutant strains, grown at appropriate temperatures, that specifically binds to the fragment containing the DNA-binding motifs. We propose that the binding protein is a repressor which is 'titrated' by this fragment when it is present in the cell on a multiple copy plasmid, thus allowing expression of phaseolotoxin genes.

Amino Acid Sequence↗
PubMed1992

Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis.

Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations.

Adult↗
PubMed1992

Superior vena cava syndrome associated with lymphoma.

OBJECTIVE: To evaluate the workup and treatment of children with lymphoma and superior vena cava syndrome. DESIGN: A retrospective survey. SETTING: State hospital serving as a secondary and tertiary referral center for pediatric oncology and pediatric cardiac surgery. PARTICIPANTS: Eleven children aged 11 months to 12 years diagnosed as having lymphoma or T-cell acute lymphoblastic leukemia who presented with superior vena cava syndrome during an 11-year period. INTERVENTIONS: Lymph node biopsy (two patients), thoracenthesis (five patients), bone marrow aspiration (two patients), and thoracenthesis in addition to bone marrow aspiration (two patients). All aspirates were evaluated with immunohistochemical studies. Chemotherapy was the only management intervention. RESULTS: T-cell lymphoma or leukemia accounted for nine cases and Hodgkin's disease for two cases. Respiratory symptoms occurred in 10 patients, including tracheal compression in six patients (compression was life-threatening in one patient). Diagnosis of superior vena cava syndrome was achieved in eight patients using surface-marker analysis of aspirates. The syndrome disappeared within 2 to 10 days. Seven of nine children whose conditions were diagnosed more than 1 year before this writing were alive and free of disease after mean follow-up of 37 months. CONCLUSIONS: (1) A specific diagnosis can be achieved in most children with superior vena cava syndrome and lymphoma; (2) Thoracic computed tomographic scans are essential, identifying minute pleural effusions that can aid diagnosis; (3) Anesthetic hazard is related only to severe tracheal compression; (4) Chemotherapy achieves excellent symptomatic relief; and (5) Long-term survival, without disease, is achievable.

Child↗
PubMed1992

The management of pediatric brain tumors in a tertiary center.

Between January 1982 and January 1990, 120 newly diagnosed pediatric patients were treated at The Chaim Sheba Medical Center. Sixty three (52.5%) tumors arose in the posterior fossa and 57 (47.5%) appeared supratentorially. A wide variety of histologic subtypes was seen, each requiring tumor-specific treatment. The modern imaging techniques-CT and MRI-offered better planning of operation, treatment and follow up. All children with highly malignant tumors were treated with combination chemotherapy besides the 'conventional radiotherapy'. Since 1987 the "eight in one day" protocol has been used extensively pre- and post-irradiation. Five-year survival, varied significantly according to tumor type, location and stage. The average delay from presentation of symptoms to diagnosis was 6 months. A multidisciplinary approach has been used in the treatment, rehabilitation and follow-up of these children. In this study, the results of treatment are presented and the role of chemotherapy is discussed.

Adolescent↗
PubMed1992

The complementary deoxyribonucleic acid sequence of guinea pig endometrial prorelaxin.

The nucleotide sequence of the relaxin gene transcript in the endometrium of the late pregnant guinea pig has been determined. The strategy used was a combination of polymerase chain reaction (PCR) with primers designed from the mRNA sequence of porcine preprorelaxin, rapid amplification of cDNA ends-PCR, and blunt end cloning in M13 mp18. With heterologous primers, a 226-basepair (bp) segment of the guinea pig relaxin gene sequence was obtained and was used to design a guinea pig-specific primer for use with the rapid amplification of cDNA ends-PCR method. The latter allowed completion of the sequence of 336 bp, with a 96-bp overlap. The sequence obtained shows greater homology at both the nucleotide and amino acid levels with porcine and human relaxins H1 and H2 than with rat relaxin, supporting the thesis that the guinea pig is not a rodent. The transcription of the guinea pig endometrial relaxin gene during pregnancy was confirmed by Northern analysis of guinea pig endometrial tissues with a species-specific cDNA probe. The endometrial relaxin gene is transcribed during pregnancy, but not in lactation, consistent with the observed immunostaining for relaxin.

Amino Acid Sequence↗
PubMed1991

Thermal stability of turnip yellow mosaic virus RNA: effect of pH and multivalent cations on RNA deaggregation and degradation.

Light scattering studies of RNA isolated from turnip yellow mosaic virus (TYMV) revealed a molar mass of 1.9.10(6) g mol-1, which is close to the value of 2.0.10(6) g mol-1 published for intact genomic TYMV RNA (2M RNA). However, gel electrophoresis under denaturing conditions demonstrated that only 30-40% of this native RNA was 2M RNA. Sucrose gradient centrifugation revealed the occurrence of a series of smaller RNA size classes, the mass ratios of which were greatly influenced by the pH of the solution and the presence of EDTA. These results suggest that native TYMV RNA preparations originally contain a mixture of intact RNA particles and of aggregates of RNA fragments with the same molar mass of about 2.10(6) g mol-1, and that the size classes are intermediates in the deaggregation process of the degraded genomic TYMV RNA. The native RNA displayed pH-dependent deaggregation and degradation. The degradation process of 2M RNA followed (pseudo) first-order kinetics. Lower degradation rates were observed for RNA depleted of divalent cations and polyamines. For depleted 2M RNA an enthalpy of activation of about 100 kJ mol-1 and an almost zero entropy of activation was calculated. Similar values were also found for depleted E. coli ribosomal RNAs and depleted MS2 RNA, demonstrating that all RNAs are equally vulnerable to degradation. In the presence of multivalent cations the activation enthalpy for 2M TYMV RNA degradation increased to 150 kJ mol-1 and the entropy of activation to 150 J K-1 mol-1, indicative for a different degradation mechanism.

Cations, Divalent↗
PubMed1991

Lack of bcr rearrangement in juvenile chronic myeloid leukemia.

Juvenile chronic myeloid leukemia (JCML) is an unusual subtype of children's leukemia, characterized by unique clinical presentation. Recent studies revealed several biological features, distinguishing from those observed in adult type chronic myeloid leukemia (ACML). The majority of ACML cases are characterized by the presence of an hybrid bcr-abl rearranged gene. In an effort to elucidate the molecular basis of this unusual leukemia we looked for bcr rearrangement in six JCML cases. No bcr rearrangement was identified in any of the analyzed samples. Together with previous studies from JCML cases, JCML has a different mechanism of leukomogenesis from ACML.

Blotting, Southern↗
PubMed1991

Dynamic light scattering by kappa- and lambda-carrageenan solutions.

The intensity correlation functions of kappa- and lambda-carrageenan in various salt solutions and at different concentrations have been determined with the help of dynamic light scattering. From the first cumulant of these correlation functions the values of the translational diffusion coefficients D have been derived. They increase with macromolecular concentration. The extrapolated values to infinite dilution of the diffusion coefficients increase with increasing salt concentration as expected from the salt concentration dependence of the r.m.s. radii of gyration determined previously by static light scattering. The translational diffusion coefficient of lambda-carrageenan in 0.1 M NaCl is smaller than the corresponding value for the kappa species. This is consistent with the difference in contour length and linear charge density of the two samples used. No satisfactory interpretation for the concentration dependence of the diffusion coefficient seems to be possible at present. Although current theories for the macromolecular and salt concentration dependence of D, taking into account charge effects, seem to be applicable, they do not allow for a consistent interpretation of the data. No specific difference between the solution behaviour of kappa- and lambda-carrageenan has been detected.

Carrageenan↗
PubMed1991

Bone marrow cell populations mimicking common acute lymphoblastic leukemia in infants with stage IV-S neuroblastoma.

Immunophenotyping of bone marrow mononuclear cells of 2 infants with stage IV-S neuroblastoma revealed the presence of many lymphoblasts and immature lymphocytes. Immunophenotyping showed that a high percentage of bone marrow cells were positive for the HLA-DR, CD19, CD20 and CD10 phenotype, similar to common acute lymphoblastic leukemia cells. Within 6 months of follow-up, without any treatment, complete regression of the tumors was observed. The coexistence of these two unusual populations will be discussed.

Bone Marrow↗
PubMed1990

A hydrodynamic study with quasielastic light scattering and sedimentation of bacterial elongation factor EF-Tu.guanosine-5'-diphosphate complex under nonassociating conditions.

The hydrodynamics of the bacterial elongation factor EF-Tu have been studied in the presence of its ligand guanosine-5'-diphosphate (GDP) by sedimentation in the ultracentrifuge and quasielastic light scattering. Sedimentation studies have made it possible to establish experimental conditions under which only negligible aggregation of the protein occurs (neutral pH, concentration less than 3 mg/mL). Analysis of the light intensity autocorrelation functions under these conditions revealed two independent scattering species with diffusion coefficients of 0.71 X 10(-6) and 0.04 X 10(-6) cm2 s-1. The material with the lower diffusion coefficient, i.e., the aggregates, represented less than 1% of the total number of EF-Tu particles. The other 99% diffused as monomeric molecules with a molar mass corresponding to the value calculated from the known primary structure of the protein. The hydrodynamic parameters derived from the experimental data suggest that EF-Tu.GDP in solution is close to a spherical particle.

Escherichia coli↗
PubMed1990

Endogenous opioid effects on abdominal muscle activity during inspiratory loading.

In a previous study in unanesthetized goats, we demonstrated that continuous naloxone (NLX) administration during inspiratory flow-resistive loading (IRL) significantly increased tidal volume (VT) but not diaphragm electromyogram (EMGdi). End-expiratory gastric pressure did increase with NLX, implying that increased abdominal muscle activity may have accounted for the NLX effect. In the current study we directly tested the hypothesis that endogenous opioid elaboration depresses the abdominal muscle response to a continuous inspiratory flow-resistive load. In seven unanesthetized goats, VT, arterial blood gases, EMGdi, and EMG activity of external oblique (EMGeo), transversus abdominis (EMGta), and external intercostal (EMGei) muscles were monitored. IRL (50 cmH2O.l-1.s) was continued for 3 h, after which NLX (0.1 mg/kg) or saline was given. Our results showed that VT decreased from 323 +/- 32 (SE) ml at baseline to 260 +/- 16 ml 5 min after the load was imposed (P less than 0.05) and further decreased to 229 +/- 18 and 217 +/- 15 ml by 120 and 180 min, respectively (180 vs. 5 min, P less than 0.05). EMGdi increased from 62 +/- 5 to 83 +/- 4% max at 5 min (P less than 0.05) but was unchanged thereafter. In contrast, for this same time period EMGeo increased from 35 +/- 5 to 58 +/- 11% max but decreased from 67 +/- 11% max at 120 min to 37 +/- 5% max at 180 min (P less than 0.05). NLX administration resulted in significant increases in EMGeo (91% above 180-min value). In contrast, EMGdi increased minimally after NLX (15% above 180-min value).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1990

[In vitro evaluation of antibacterial activity of the original oxime type of beta-lactam antibiotics with the 4-aminobenzensulfonamide group].

Four newly prepared beta-lactam antibiotics of the oxime type with a 4-aminobenzensulphonamidogroup, synthetized at the Research Institute for Pharmacy and Biochemistry, Prague, were subjected to an evaluation of antibacterial efficacy in vitro. The evaluation was carried out by determining the minimal inhibitory concentration (MIC) in 47 clinical strains and 6 standard strains (Staphylococcus aureus, Streptococcus pyogenes and facecalis, E. coli, Enterobacter and Proteus spec., Pseudomonas aeruginosa). The results were compared with the MIC of cefalexin, cefoxitin, cefazolin, cefsulodin, and ampicillin. The antibacterial effect of these agents was lower than that of the compared antibiotics. It was slightly better in the pseudomonadic strains, where the efficacy of cefusulodin was best and the other four antibiotics appeared to be worst.

Ampicillin↗