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I Goldman

Publications and source records attributed to I Goldman.

18 recordsLinked to original sources
PubMed2001

Evidence for clonal propagation in natural isolates of Plasmodium falciparum from Venezuela.

We have analyzed 75 isolates of Plasmodium falciparum, collected in Venezuela during both the dry (November) and rainy (May-July) seasons, with a range of genetic markers including antigen genes and 14 random amplified polymorphic DNA (RAPD) primers. Thirteen P. falciparum stocks from Kenya and four other Plasmodium species are included in the analysis for comparison. Cross-hybridization shows that the 14 RAPD primers reveal 14 separate regions of the parasite's genome. The P. falciparum isolates are a monophyletic clade, significantly different from the other Plasmodium species. We identify three RAPD characters that could be useful as "tags" for rapid species identification. The Venezuelan genotypes fall into two discrete genetic subdivisions associated with either the dry or the rainy season; the isolates collected in the rainy season exhibit greater genetic diversity. There is significant linkage disequilibrium in each seasonal subsample and in the full sample. In contrast, no linkage disequilibrium is detected in the African sample. These results support the hypothesis that the population structure of P. falciparum in Venezuela, but not in Africa, is predominantly clonal. However, the impact of genetic recombination on Venezuelan P. falciparum seems higher than in parasitic species with long-term clonal evolution like Trypanosoma cruzi, the agent of Chagas' disease. The genetic structure of the Venezuelan samples is similar to that of Escherichia coli, a bacterium that propagates clonally, with occasional genetic recombination.

Animals↗
PubMed1999

Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum isolates from Venezuela.

The present study was designed to characterize mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum in the Bolivar region of Venezuela, where high levels of clinical resistance to sulfadoxine-pyrimethamine (SP, Fansidar; F. Hoffman-La Roche, Basel, Switzerland) has been documented. We used a nested mutation-specific polymerase chain reaction and restriction digestion methods to measure 1) the prevalence of DHFR mutations at 16, 50, 51, 59, 108, and 164 codon positions, and 2) the prevalence of mutations in the 436, 437, 581, and 613 codon sites in DHPS gene. In the case of the DHFR gene, of the 54 parasite isolates analyzed, we detected the presence of Asn-108 and Ile-51 in 96% of the isolates and Arg-50 mutation in 64% of the isolates. Each of these mutations has been associated with high level of resistance to pyrimethamine. Only 2 samples (4%) showed the wild type Ser-108 mutation and none showed Thr-108 and Val-16 mutations that are specific for resistance to cycloguanil. In the case of DHPS gene, we found a mutation at position 437 (Gly) in 100% of the isolates and Gly-581 in 96% of the isolates. The simultaneous presence of mutations Asn-108 and Ile-51 in the DHFR gene and Gly-437 and Gly-581 in the DHPS gene in 96% of the samples tested suggested that a cumulative effect of mutations could be the major mechanism conferring high SP resistance in this area.

Animals↗
PubMed1998

CCR5 coreceptor usage of non-syncytium-inducing primary HIV-1 is independent of phylogenetically distinct global HIV-1 isolates: delineation of consensus motif in the V3 domain that predicts CCR-5 usage.

The cellular tropism of human immunodeficiency virus type 1 (HIV-1) is dependent on utilization of specific chemokine co-receptor: macrophage-tropic/non-syncytium-inducing (NSI) viruses use CCR5, whereas T-cell tropic/syncytium-inducing (SI) viruses preferentially use CXCR4. We have analyzed co-receptor usage of 24 phylogenetically distinct primary HIV-1 isolates representing group M (clades A-F) and group O with known SI and NSI phenotype, using lymphocytes from donor with nonfunctional CCR5 (CCR5-/-; homozygous 32-bp deletion). While all SI isolates infected CCR5-/- lymphocytes (and hence do not require CCR5 for viral entry), all NSI isolates, regardless of clade, did not infect CCR5-/- lymphocytes. Thus, CCR5 expression is required for infection with NSI isolates and the CCR5 usage is independent of viral genotype. To localize the viral determinant involved in CCR5 binding, the V3 sequences across the clades were aligned based on the CCR5 usage. There were conserved uncharged residues at position 11 of V3 (mostly serine/glycine) and negatively charged residues at residue 25 (mostly glutamic/aspartic acid) among all isolates that used CCR5, whereas substitution with arginine or glutamine at these two positions led to usage of a co-receptor other than CCR5. This analysis led us to identify a consensus motif S/GXXXGPGXXXXXXXE/D within the V3 loop that predicts CCR5 co-receptor usage. Most isolates, with exception of one isolate, containing the conserved motif and predicted to utilize CCR5 indeed had an absolute requirement of CCR5 expression for infectibility. Site-directed mutagenesis in the infectious molecular clone further confirmed these results. Taken together, these data provide evidence that sequences within the V3 loop provide important residues that might be directly or indirectly involved in binding to a CCR5 co-receptor.

Amino Acid Sequence↗
PubMed1993

Evidence for mother-to-child transmission of human T lymphotropic virus type II.

Serologic analysis of the children of 2 married human T lymphotropic virus type II (HTLV-II)-infected prostitutes demonstrated antibodies to HTLV-II in an 8-year-old boy whose only recognizable risk for HTLV-II infection was breast-feeding during his first 4 years of life. Limited sequence analysis of isolates infecting the mother and child demonstrated 100% identical sequences in the long terminal repeat (LTR65-297; 236 bp), pol4762-4919 (157 bp), and env5523-6003 (480 bp) regions (both isolates were subtype a), suggesting mother-to-child transmission. In contrast, isolates obtained from 2 other prostitutes from the same geographic region had sequences different from those of the first woman and her child, and the second and third women were infected with HTLV-II subtype b. Although vertical transmission of HTLV-II in this 8-year-old child cannot be conclusively ascertained, the probability is overwhelming that infection occurred through breast-feeding for an extended period of time.

Adolescent↗
PubMed1993

A randomized comparative study of the electrophysiological and electrocardiographic effects of isradipine vs verapamil.

Isradipine is a new dihydropyridine calcium antagonist reported to have minimal effects on cardiac electrophysiology. Of 19 patients with normal cardiac electrophysiological profiles, 11 received isradipine intravenously at doses of 0.0010, 0.0020, 0.0040 and 0.0080 mg.kg-1 (0.0150 mg.kg-1 total dose), and eight received verapamil intravenously at 0.0125, 0.0250, 0.0500 and 0.1000 mg.kg-1 (0.1875 mg.kg-1 total dose). One patient experienced hypotension several minutes after receiving the third isradipine dose. With isradipine, systolic blood pressure (BP) decreased from 154 +/- 24 to 151 +/- 22, 143 +/- 25, 133 +/- 19 and 124 +/- 17 mmHg, respectively. Diastolic BP decreased from 83 +/- 10 (baseline) to 80 +/- 12, 76 +/- 10, 74 +/- 7 and 68 +/- 9 mmHg, respectively. With verapamil, systolic BP changed from 132 +/- 20 (baseline) to 135 +/- 29, 132 +/- 24, 130 +/- 25 and 115 +/- 17 mmHg, respectively, and diastolic BP changed from 80 +/- 14 to 84 +/- 14, 81 +/- 9, 78 +/- 6 and 73 +/- 5 mmHg, respectively. Isradipine had no significant effect on the PR, QRS, QT and QTc intervals, nor were there changes in the atrial-His (AH) and His-ventricle (HV) intervals, atrioventricular nodal effective refractory period. Wenckebach cycle length or sinus node recovery time. Similarly, verapamil at the doses studied did not significantly affect PR, QRS, QT, QTc, AH or HV intervals. However, with verapamil, the Wenckebach cycle length changed significantly from 394 +/- 82 (baseline) to 448 +/- 93 ms. Despite the significant fall in BP with isradipine, heart rate did not change significantly. These results support the electrophysiological neutrality of isradipine on the cardiac conduction system.

Adult↗
PubMed1979

Colony growth of T lymphocytes in vitro. Control and regulation of clonal formation.

Human lymphocytes stimulated with PHA in liquid phase (step 1) and then seeded in a two-layer soft agar system (step 2) grew and developed into T cell colonies. Colony formation was enhanced when the agar culture was supplemented with culture fluid obtained from phytohemagglutin-treated lymphocytes (Ly-CF). Untreated lymphocytes plated directly in the soft agar system also developed into colonies if the culture medium contained Ly-CF. Mitogen-sensitized T lymphocytes produced a lymphocyte colony enhancing factor in the culture fluid which stimulated lymphocytes into colony formation. The best plating efficiency (1:250) was attained when blood mononuclear cells were seeded. When spleen cell culture fluid or a highly concentrated blood-adherent cell population was added to the soft agar, colony development was strongly inhibited. Monocytes-macrophages secrete a lymphocyte colony inhibiting factor in the culture medium. These lymphokines exert a competitive influence on T cells and thus control and regulate clonal proliferation.

Agar↗
PubMed1978

Partial purification and characterization of the human lymphocyte colony enhancing factor (LCEF).

The cloning potential of PHA-treated T cells is significantly enhanced when lymphocyte culture fluid (LCF) from mitogen-treated lymphocytes is added to the soft agar culture system. The mitogens seem to stimulate the release of a lymphocyte colony enhancing factor (LCEF) into the culture medium. A study of the physico-chemical properties of the LCEF revealed that it is a nondialyzable, heat-labile molecule which migrates in the haptoglobin (2--2) post-transferrin region in acrylamide electrophoresis. It is stable to RNase and DNase but labile to papain and trypsin. The LCEF was partially purified from the crude LCF using a sequence of techniques--ammonium sulphate precipitation, DEAE-cellulose and Bio-Gel P-150 chromatography and disc electrophoresis. The mol. wt of the purified LCEF, determined from gel filtration chromatography, was 90,000--110,000.

Clone Cells↗
PubMed1977

Effects of actodigin on the heart.

Actodigin is a new semisynthetic cardiac glycoside reported to have a rapid onset and brief duration of action in dogs. Five patients with congestive heart failure in normal sinus rhythm were given incremental doses of actodigin. Overall, there was no significant change in heart rate, aortic or pulmonary artery pressure, systemic vascular resistance, cardiac index, and stroke volume. This lack of response to actodigin is consistent with previous reports of acute administration of other cardiac glycosides. Four patients with atrial fibrillation and a rapid ventricular rate were given similar doses of actodigin. The ventricular rate was readily controlled. After drug administration was stopped, the ventricular rate quickly returned toward predrug levels. Thus, the rapid onset and brief duration of action of actodigin may be useful in the initial management of atrial fibrillation.

Adult↗