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Biomedical subjects

M Mandel

Publications and source records attributed to M Mandel.

At least 91 records · Page 5Linked to original sources
PubMed1990

[In vitro antibacterial activity of new oxime type of beta-lactam antibiotics].

The antibacterial efficacy of two novel beta-lactam antibiotics of the oxime type, VUFB 16265 and 16272, was evaluated by determining the minimal inhibitory concentration (MIC) in 47 clinical strains and 6 standard strains (Staphylococcus aureus, Streptococcus pyogenes and faecalis, E. coli, Enterobacter and Proteus spec., Pseudomonas aeruginosa), which were the most frequent causes of infectious complications. The results were compared with the MIC of cefalexin, cefoxitin, cefazolin, cefsulodin, and ampicillin. The antibacterial activity of both VUFB drugs was comparable with the efficacy of the antibiotics tested. Only in the strains of Pseudomonas aeruginosa the activity of all antibiotics under evaluation was low and only cefsulodin was effective.

Ampicillin↗
PubMed1989

Immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukaemia: correlation with clinical stage.

A search for a correlation between the clinical stage of chronic lymphocytic leukaemia (CLL) and the pattern of immunoglobulin heavy chain gene rearrangements was undertaken. DNA samples from the leukaemic cells of 38 CLL patients were analysed by Southern blot hybridization. Using probes for the immunoglobulin heavy chain J (JH) and C mu regions a marked heterogeneity of the hybridization patterns was observed in both regions. The number of JH hybridization bands varied from one to four and more than two were found in 58% of the patients. In 42% of the patients no germline JH genes were found. One to three additional C mu bands were observed in 34%, but the germline was preserved in all samples. There was no correlation between the clinical stage and the number of hybridizing JH bands; however, a significant correlation was found between the loss of JH germline band or a C mu multiband pattern and advanced stage of the disease. The genetic events in the immunoglobulin genes observed in advanced CLL patients are assumed to result from clonal evolution and tumour progression.

Adult↗
PubMed1989

Aplastic crisis due to human B19 parvovirus infection in red cell pyrimidine-5'-nucleotidase deficiency.

Two siblings with chronic hemolytic anemia due to red cell pyrimidine-5'-nucleotidase (P-5'-N) deficiency, presented within a few days of each other with a febrile illness and pancytopenia. The cause of the aplastic crisis was an acute infection with human B19 parvovirus (B19 HPV) as proven by immunoelectron microscopy and DNA hybridization. This is the first report on the association of B19-HPV-related aplastic crisis with P-5'-N deficiency.

5'-Nucleotidase↗
PubMed1989

Pure red cell hypoplasia associated with polyglandular autoimmune syndrome type I.

The polyglandular autoimmune syndrome Type I is characterized by hypoparathyroidism, adrenal insufficiency, and mucocutaneous candidiasis, and may be associated with other autoimmune-mediated diseases, including pernicious anemia, chronic active hepatitis and vitiligo. We report two patients aged 7 and 15 years in whom pure red cell hypoplasia was a prominent feature of the polyglandular Type I syndrome. Hematological remission was obtained with corticosteroid treatment in one patient, and with gamma-globulin therapy in the other. These findings indicate that pure red cell hypoplasia is one of the autoimmune manifestations that may be associated with this syndrome.

Adolescent↗
PubMed1989

A search for bcl1, bcl2, and c-myc oncogene rearrangements in chronic lymphocytic leukemia.

Three cellular or putative oncogenes: c-myc, bcl1, and bcl2 were previously found to be rearranged in some B cell malignancies due to chromosomal translocations. Data concerning the role of such genetic rearrangements in B-CLL are very scanty and limited to few cases in which bcl1 rearrangements were found. We studied DNA samples from 38 cases of B-CLL by Southern blot technique in order to find out the existence and frequency of such events. No bcl1 or bcl2 rearrangements were found in any of the studied cases; thus, involvement of these genes in CLL must be rare. In one patient who had an aggressive and resistant disease, c-myc rearrangement was found.

Adult↗
PubMed1988

Cloning of cDNA encoding a 32-kDa protein. An accessory polypeptide of the H+-ATPase from chromaffin granules.

The purified H+-ATPase from chromaffin granules is composed of several polypeptides, one of which has an apparent molecular weight of 39,000. Immunoblots with the antibody against this protein and various membrane preparations showed that similar or even identical polypeptides may be associated with the H+-ATPases from synaptic vesicle, kidney microsomes, and lysosomes. A cDNA library was constructed from bovine adrenal medulla, and the cDNA encoding the polypeptide was isolated and sequenced. Search in DNA and protein data banks revealed no significant homology to known genes. Hydrophobicity plot revealed no obvious transmembrane segments with the exception of one stretch of hydrophobic and neutral amino acid starting at leucine 16. The cDNA was shown to encode the entire polypeptide by the virtue of an amino acid sequence corresponding to the N terminus of the open reading frame and by subunit and site-specific antibodies. The cDNA was cloned into an expression vector, transcribed by T7 polymerase, and translated by reticulocyte lysate. Even though the cDNA encodes a protein with a molecular weight of 31,495, the translation product comigrated on sodium dodecyl sulfate gels with the subunit of the purified H+-ATPase. In line with several other subunits of vacuolar H+-ATPases, no signal sequence was detected in the translated gene. Northern blots revealed the presence of a single mRNA of about 1.6 kb in bovine adrenal medulla. However, liver, lung, and kidney may contain additional mRNA of about 1.7 kb.

Adrenal Medulla↗
PubMed1988

cDNA sequence encoding the 16-kDa proteolipid of chromaffin granules implies gene duplication in the evolution of H+-ATPases.

Vacuolar H+-ATPases function in generating protonmotive force across the membranes of organelles connected with the vacuolar system of eukaryotic cells. This family of H+-ATPases is distinct from the two other families of H+-ATPases, the plasma membrane-type and the eubacterial-type. One of the subunits of the vacuolar H+-ATPase binds N,N'-dicyclohexylcarbodiimide (DCCD) and has been implicated in the proton-conducting activity of these enzymes. We have cloned and sequenced the gene encoding the DCCD-binding protein (proteolipid) of the H+-ATPase of bovine chromaffin granules. The gene encodes a highly hydrophobic protein of 15,849 Da. Hydropathy plots revealed four transmembrane segments, one of which contains a glutamic residue that is the likely candidate for the DCCD binding site. Sequence homology with the vacuolar proteolipid and with the proteolipids of eubacterial-type H+-ATPases was detected. The proteolipids from Escherichia coli, spinach chloroplasts, and yeast mitochondria matched better to the NH2-terminal part of the vacuolar protein. The proteolipids of bovine mitochondria and Neurospora mitochondria matched better to the COOH-terminal end of the vacuolar proteolipid. These findings suggest that the proteolipids of the vacuolar H+-ATPases were evolved in parallel with the eubacterial proteolipid, from a common ancestral gene that underwent gene duplication.

Amino Acid Sequence↗
PubMed1988

More than two immunoglobulin heavy chain J region genes in the majority of infant leukemia.

Congenital and infant leukemia are rare conditions associated with a very poor prognosis due to the high frequency of adverse clinical and laboratory parameters. As the occurrence of multiple immunoglobulin heavy chain hybridization band in childhood leukemia has been associated with poor prognosis, we studied whether it was present in this type of leukemia as well. Seven cases were examined, 4 of them less than 7 months of age. The immunophenotype was lymphoid in 5 and hybrid in 2. Most had abnormal karyotypes. In 5 of the 7, including all with congenital leukemia, an immunoglobulin heavy chain J region multiband pattern was found by Southern blot. The multiband pattern, whether primary or due to clonal evolution, seems to be associated with poor prognosis.

Adolescent↗
PubMed1986

Length and sequence polymorphisms in the ribosomal gene spacer of the Hawaiian sea urchin, T. gratilla.

Blot-hybridization of sea urchin (Tripneustes gratilla) genomic DNA with a cloned rDNA probe revealed individual variation in the length of the rDNA repeat unit and also in the non-transcribed spacer sequences. The number of distinct rDNA repeat subclasses distinguishable within any one sea urchin was limited and usually 2 to 3. However, examination of a number of sea urchins indicated a large number of distinct rDNA repeat types in the population as a whole; all of the rDNA repeat types in nine individuals were different. The presence of limited heterogeneity in the rDNA repeats of single individuals, with may different repeat types in the population as a whole, suggests that rDNA variants can be rapidly and selectively propagated within a chromosomal lineage.

Animals↗
PubMed1985

Structural analysis of ribosomal RNA genes from the Hawaiian sea urchin species, Tripneustes gratilla.

Ribosomal gene sequences (rDNA) were isolated from the genomic DNA of the Hawaiian sea urchin Tripneustes gratilla by cloning in plasmid and phage vectors. The rRNA coding regions in four clones were localized by hybridizing Southern transfers of endonuclease-digested DNA with 32P-labeled 26S rRNA and 32P-labeled 18S rRNA. Three of the rDNA clones were isolated from a library of DNA from a single sea urchin and represent the two major types of rDNA repeats present in that individual's genome. Both repeat types appear identical within their rRNA coding regions but are dissimilar in an area of the nontranscribed spacer (NTS) adjacent to the 3' end of the 26S coding region. The cloned rDNA repeats were shorter than their genomic counterparts due to deletions occurring within internally repetitious NTS domains, probably as a result of unequal recombination during phage propagation.

Animals↗
PubMed1983

Molecular cloning of five individual stage- and tissue-specific mRNA sequences from sea urchin pluteus embryos.

Five developmentally regulated sea urchin mRNA sequences which increase in abundance between the blastula and pluteus stages of development were isolated by molecular cloning of cDNA. The regulated sequences all appeared in moderately abundant mRNA molecules of pluteus cells and represented 4% of the clones tested. There were no regulated sequences detected in the 40% of the clones which hybridized to the most abundant mRNA, and the screening procedures were inadequate to detect possible regulation in the 20 to 30% of the clones presumably derived from rare-class mRNA. The reaction of 32P[cDNA] from blastula and pluteus mRNA to dots of the cloned DNAs on nitrocellulose filters indicated that the mRNAs complementary to the different cloned pluteus-specific sequences were between 3- and 47-fold more prevalent at the pluteus stage than at the blastula stage. Polyadenylated RNA from different developmental stages was transferred from electrophoretic gels to nitrocellulose filters and reacted to the different cloned sequences. The regulated mRNAs were undetectable in the RNA of 3-h embryos, became evident at the hatching blastula stage, and reached a maximum in abundance by the gastrula or pluteus stage. Certain of the clones reacted to two sizes of mRNA which did not vary coordinately with development. Transfers of RNA isolated from each of the three cell layers of pluteus embryos that were reacted to the cloned sequences revealed that two of the sequences were found in the mRNA of all three layers, two were ectoderm specific, and one was endoderm specific. Four of the regulated sequences were complementary to one or two major bands and one to at least 50 bands on Southern transfers of restriction endonuclease-digested total sea urchin DNA.

Animals↗
PubMed1982

Aphasia in a prelingually deaf woman.

A left parietal infarct in a prelingually deaf person resulted in an aphasia for both American Sign Language (ASL) and written and finger-spelled English. Originally the patient had a nearly global aphasia affecting all language systems. By five to seven weeks post-onset her symptoms resembled those of hearing aphasics with posterior lesions: fluent but paraphasic signing, anomia, impaired comprehension and repetition, alexia, and agraphia with elements of neologistic jargon. In addition, there was a pronounced sequential movement copying disorder, reduced short-term verbal memory and acalculia. In general, the patient's sign errors showed a consistent disruption in the structure of ASL signs which parallels the speech errors of oral aphasic patients. We conclude that most aphasic symptoms are not modality-dependent, but rather reflect a disruption of linguistic processes common to all human languages. This case confirms the importance of the left hemisphere in the processing of sign language. Furthermore, the results indicate that the left supramarginal and angular gyri are necessary substrates for the comprehension of visual/gestural languages.

Aged↗
PubMed1982

Fecal mutagens in two Japanese populations with different colon cancer risks.

Human feces from 223 Japanese in Hawaii at high risk for colon cancer and feces from 166 Japanese of northern rural Japan at low risk for colon cancer were shown to contain mutagenic activity under five different test conditions. The first assay, using the Ames TA98 and TA100 Salmonella test, detected ether-soluble mutagens in the presence and absence of rat liver microsomes. Of these, the TA98 direct-acting mutagens are present more frequently in the feces of the high-risk population than the low-risk population at a high level of statistical significance (p less than 0.01). TA98 mutagens activated by rat liver microsomes also occur significantly more frequently in the feces of the Japanese from Hawaii (p less than 0.05). Mutagens detected by TA100 in the presence and absence of rat liver microsomes are not commonly found in either Japanese population. The second bacterial test system used to detect fecal mutagens uses Escherichia coli rec-. This system detects water-soluble fecal mutagens which are also present more frequently in the high-risk population than in the low-risk population (p less than 0.05).

Age Factors↗
PubMed1981

An evaluation of tests using DNA repair-deficient bacteria for predicting genotoxicity and carcinogenicity. A report of the U.S. EPA's Gene-TOX Program.

The detection of DNA-damaging agents by repair-deficient bacterial assays is based on the differential inhibition of growth of repair-proficient and repair-deficient bacterial pairs. The various methodologies used are described and recommendations are made for their improved use. In a survey of the literature through April 1979, 91 of 276 papers evaluated contained usable data, resulting in an analysis of 611 compounds that had been assayed in 1 or more of 55 pairs of repair-proficient and repair-deficient strains. The results indicate that (1) a liquid suspension assay is more sensitive than a spot (diffusion) test. In a review of the Escherichia coli polA assay, 45 compounds that gave "No Test" in the spot test were clearly positive or negative in the liquid suspension assay. (2) Of the 21 compounds analyzed by the E. coli polA assay and by other E. coli repair-deficient strains (e.g., rec, uvr, hcr, and exr derivatives of WP2 and AB1157), 10 were in complete agreement in all strains except uvrA strains. This indicates that strains other than polA+/polA- are useful for detecting DNA-damaging agents. However, in selecting strains for use in these assays, care should be taken to consider repair pathway specificity for particular compounds. (3) There was a 78% correspondence between results obtained with E. coli polA and Bacillus subtilis (H17/M45, 17A/45T) rec assay and between E. coli polA and Proteus mirabilis. (4) In a comparison of test results with carcinogenicity data, 44 of 71 (62%) carcinogenic compounds assayed by the polA system were positive, 10 (14%) were negative, and 17 (24%) gave No Test or doubtful results. 7 carcinogens were assayed by other E. coli strains and all were positive. 56 carcinogens were assayed in B. subtilis: 24 (43%) were positive, 9 (16%) were negative, and 23 (41%) gave No Test or doubtful results. Of the 7 carcinogens assayed in P. mirabilis, 6 (86%) were positive and 1 (14%) was negative. (5) The results were analyzed with respect to chemical classes. E. coli polA detected the highest percentage of hydroxylamines and alkyl epoxides. The B. subtilis rec assay detected the highest percentage of nitrosamines and sulfur and nitrogen oxides. It is concluded that some of these test systems are effective tools for the detection of DNA-damaging and potentially carcinogenic compounds, especially if the assay is done in liquid suspension and if more than 1 pair of tester strains is used. Advantages and disadvantages of the assay are discussed and suggestions are made for improvements in the system.

Animals↗
PubMed1981

Replication of simian virus 40 DNA in normal human fibroblasts and in fibroblasts from xeroderma pigmentosum.

Simian virus 40 infection of semipermissive human diploid fibroblasts (HF), at early passage in cell culture, was compared with that of permissive established monkey cell lines. Viral DNA can be readily detected at 24 to 48 h postinfection at 37 degrees C with a high multiplicity of infection, approaching 10% of that of monkey cells (TC7). The length of time necessary for replication of an average molecule of viral DNA was found to be indistinguishable in HF and TC7 cells. Strand elongation plus termination were assessed by following the accumulation of DNA I at 40 degrees C from replicative intermediates of tsA30 prelabeled at 33 degrees C, obviating isotope pool problems. Combined initiation and elongation of wild-type viral DNA was measured by density shift experiments involving a 5-bromodeoxyuridine chase of prelabeled [3H]thymidine-labeled viral DNA. Determination of accumulation of viral T and V antigens supports the conclusion that the most likely basis for the reduced virus yield in HF cells results from the inefficiency of an early stage in virus infection, before or during uncoating. Similar results were obtained in fibroblasts derived from patients with xeroderma pigmentosum, suggesting that enzymes of UV repair are not required in unirradiated simian virus 40 DNA synthesis.

Animals↗