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Biomedical subjects

S Ali

Publications and source records attributed to S Ali.

At least 307 records · Page 17Linked to original sources

Intrinsic polymorphism of variable number tandem repeat loci in the human genome.

In the human genome, short tandem repetitive (STR) DNA sequences often show restriction fragment length polymorphisms (RFLPs) due to variation in the number of copies of the repeat unit. For a subset of these sequences known as minisatellites or variable number tandem repeat loci (VNTR), it has been proposed that a homologous "core" sequence of 10-12 nucleotides is involved in the mechanism(s) generating the polymorphism. In our present study we have prepared oligonucleotide probes complementary to one or two repeat units of several VNTR loci. Under stringent hybridization and wash conditions these probes hybridize locus specifically thus allowing the evaluation of the intrinsic polymorphism of individual loci. Our results indicate that not all of the loci having STR DNA sequences are polymorphic despite the fact that they share the "core" sequence. This suggests that more than the DNA sequence of the locus is involved in the mechanism(s) generating the polymorphism.

Alleles↗

Characterization of the gene encoding ovine beta-lactoglobulin. Similarity to the genes for retinol binding protein and other secretory proteins.

Beta-lactoglobulin is the major whey protein in the milk of ruminants and is expressed in the mammary gland during pregnancy and lactation. Here we describe the isolation and characterization of genomic clones encoding ovine beta-lactoglobulin. Two very similar but non-identical, types of beta-lactoglobulin clone were obtained. DNA sequence analysis of one of these showed that the gene is 4900 bases long and contains seven exons. It codes for a protein of 180 amino acid residues, containing an 18-residue signal peptide, within exons I to VI; exon VII is non-coding. We show that the genes encoding serum retinol binding protein, major urinary protein, alpha-1-acid glycoprotein and apolipoprotein D have a similar organization of exons and introns to beta-lactoglobulin. In particular, a comparison between beta-lactoglobulin and retinol binding protein shows that both genes encode equivalent elements of three-dimensional protein structure within analogous exons. These proteins are all members of a large, diverse family of secretory proteins, many of which function in binding small hydrophobic molecules.

Amino Acid Sequence↗

Chromosome 9 of Ellobius lutescens is the X chromosome.

Ellobius lutescens carries an apparently identical karyotype (2n = 17) in both sexes. On the basis of indirect evidence the unpaired chromosome 9 has been considered to represent the X chromosome of this species. We have obtained data to substantiate this view by four different techniques. After fusion of HPRT- RAG cells with E. lutescens fibroblasts we demonstrated that the enzymes HPRT and G6PD are localized on the presumptive X chromosome. By analysis of pachytene figures after silver staining we showed by electron microscopy that the single chromosome exhibits the typical features of an X chromosome in male meiosis. Hybridization of (GATA)4 and (GACA)4 oligonucleotide probes to E. lutescens DNA revealed several distinct bands in the high molecular weight range some of which appeared to be specific for the individual but not for the sex of the animal. Hybridization in situ of the (GATA)4 probe on metaphase spreads of E. lutescens did not highlight any particular chromosome segment but showed a significant deficit of these sequences in chromosome 9. These observations are discussed with respect to their bearing on X chromosome determination. Finally it is concluded that E. lutescens should be an ideal tool for testing candidate genes assumed to be involved in primary sex determination.

Animals↗

Susceptibility of Plasmodium falciparum to chloroquine and mefloquine in Somalia.

A field study was conducted in the Malable area, in Somalia, to assess the susceptibility of Plasmodium falciparum to chloroquine and mefloquine. The in vivo response of P. falciparum to standard therapeutic regimen of chloroquine was studied in 16 children (1-12 years) using the standard WHO in vivo field test. All subjects were parasite free by day 3 and no recrudescence occurred during a 7-d follow-up. In the 24 h micro in vitro tests for chloroquine, 29 of 39 tests performed were successful. Of the 29 isolates, 3 showed distinct resistance and 2 were borderline. The drug concentration yielding 99% (EC99) inhibition was 1.64 x 10(-6) M, indicating low grade resistance. For mefloquine, 11 of 20 tests gave interpretable results and were sensitive, although with some heterogeneity. The EC50 and EC99 of 0.24 x 10(-6) M and 1.31 x 10(-6) M respectively indicate sensitivity.

Adolescent↗

Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies.

Investigation of the biodistribution of subtherapeutic amounts of a new, chromatographically purified rhenium-186(tin) hydroxyethylidene diphosphonate radiopharmaceutical have been completed in five patients with metastatic carcinoma to bone. The new agent localizes in metastatic foci in bone in the same manner as do standard technetium-99m diphosphonate bone-scanning agents and appears able to deliver therapeutic radiation doses of thousands of rads (tens of grays) to these metastatic foci while limiting the total red marrow dose to less than 75 rad (0.75 Gy). The simultaneous treatment of multiple metastatic foci in bone appears feasible with this new agent.

Adult↗

Antagonistic effect of zinc in lead treated developing chick embryos.

Lead (50 micrograms) and zinc (100 & 200 micrograms) alone and in combination, were injected on 7th day of incubation into the yolk sac of developing chick embryos. The deformities induced by Pb alone included reduced hatchability, growth retardation, hydrocephalus, defective beak and legs, microphthalmia, anophthalmia and curling of hair. The concurrent exposure with Zn (200 micrograms), however, provided a remarkable protection against lead induced deformities, reflected in terms of almost normal development of chick embryos with increased hatchability and lower incidences of malformations, and mortality.

Abnormalities, Drug-Induced↗

Protective role of calcium in lead toxicity during development of chick embryo.

In the present study the interaction of lead (Pb) and calcium (Ca) during embryogenesis was investigated. Lead (50 micrograms) alone and in combination with Ca (100 micrograms, 500 micrograms and 1000 micrograms) was injected on seventh day of incubation into the yolk sac of developing chick embryos. Treatment with lead alone caused stunted growth in chick embryos with several deformities e.g. defective beak and legs, hydrocephalus, microphthalmia and anophthalmia. The combined treatment of Pb with Ca showed a remarkable protective effect against lead induced deformities characterized by development of chick embryos with a low incidence of deformities.

Abnormalities, Drug-Induced↗

Development of a single probe for documentation of chimerism following bone marrow transplantation.

Although numerous genetic markers are available for studying chimerism after bone marrow transplantation (BMT), there remains a need for a practical and highly informative method that is applicable in the early posttransplantation period. Using DNA restriction-fragment-length polymorphisms (RFLPs), we have evaluated the feasibility of developing a single synthetic oligonucleotide probe to study post-BMT chimerism. We have thus tested three candidate probes, termed O-3315-32, O-3315-80, and O-AY-29, that are homologous to tandemly repetitive sequences. Our results demonstrated donor-specific and recipient-specific fragments in 11 of 11 HLA-matched sibling pairs tested using probes O-3315-32 and O-3315-80. When probe O-AY-29 was used, 14 of 17 sibling pairs showed both donor and recipient markers, one had only a recipient marker, and two were identical. We showed that each of the three synthetic probes was effective in documenting donor marrow engraftment, mixed hematopoietic chimerism, the patient's pre-BMT phenotype (by using cultured skin fibroblasts obtained after BMT), and the origin of the malignant hematopoietic cells (i.e., of donor or recipient origin) in patients who developed recurrent hematologic malignancy following BMT. Compared with the use of cloned genomic probes, there are several important advantages to the use of synthetic oligonucleotide probes in studying post-BMT chimerism. Synthetic probes have absolute hybridization specificity and can be designed to suit the purposes of an individual study, since they have adjustable specificity that can be altered by changes in the length of the probe and by changes in the hybridization temperature. A single synthetic probe analogous to several highly polymorphic loci can have a polymorphism information content sufficiently high so that all but a small percentage of BMT patients could be followed easily; for example, if a probe were complementary to three highly polymorphic unlinked loci, it would discriminate approximately 98% of sibling donor/recipient pairs. This would be accomplished using only one restriction-endonuclease digestion and only one gel electrophoresis. Since other genetic markers, e.g., red blood cell antigens, immunoglobulin allotypes, and chromosome analysis, are not uniformly informative and, in some cases, cannot be used in the early posttransplantation period, the use of synthetic oligonucleotide probes for analysis of DNA RFLP is emerging as the method of choice for studies of post-BMT chimerism. This method will allow for the development of new knowledge that has not been possible with previous methods.

Bone Marrow↗

[Developmental profile of scintigraphic parameters within 3 weeks following primary myocardial infarction without any attempt at revascularization].

30 patients with a transmural primary myocardial infarction conventionally treated, are explored by myocardial scintigraphy using thallium 201, and calculation of a lesional score (L.S) and angio-scintigraphy on the first day (D1) and at three weeks (D21). The results of these examinations are compared to those of coronography at D21. Anterior necroses present a myocardial fixation defect and a dysfunction of the left ventricle which are more severe than in inferior necroses. Patients with a marked fixation defect (L.S 2) at D1, present a low ejection fraction (EF) becoming significantly worse at D21. Coronary permeability is accompanied by an appreciable improvement of the myocardial fixation from D1 to D21 and a stability of EF. On the contrary, if the occlusion persists, the fixation defect is stable and the EF decreases significantly. In this study, the coronary permeability appears to be associated to a perservation of the ischemic myocardium which may only be demonstrated by knowing the evolution of the various parameters during the first three weeks of the infarction.

Coronary Angiography↗

Leukemic cells arise from cloned cytotoxic lymphocytes during cell culture.

In spite of many promising attempts to apply T cell clones to questions of in vitro and in vivo function of T cells it is still unclear to what extent continuous propagation of T lymphocytes in vitro effects their original properties. This study describes the appearance of malignant cells from long-term cultured C57BL/6 (B6) cytotoxic T lymphocytes (CTL). Four out of five T cell lines (CTLL.1,3,4,5) representing distinct stages of development of T effector cells in vitro were repeatedly cloned and all five CTLL were tested for various cellular parameters. It is shown that transformation of H-Y-specific CTLL into malignant cells in vitro was accompanied by alterations in growth characteristics, successive loss of specificity and cytolytic function and by quantitative changes in the expression of cell surface markers. Whereas growth of the H-Y-specific CTLL (CTLL.1) was dependent on antigen and concanavalin A (Con A) supernatant (Con ASN) the CTLL variants could be either maintained in Con ASN alone (CTLL.3) or in the absence of both antigen and lymphokine sources (CTLL.4,5). CTLL.1 was cytolytic for male B6 target cells and lysed P815 tumor targets in the presence but not the absence of lectin. In contrast, CTLL.3 lost its original specificity but lysed P815 cells in the absence or presence of lectin. CTLL.2 representing an intermediary stage showed cytolytic activity on both male B6 and P815 target cells. In contrast, CTLL.4 and CTLL.5 lost the ability to lyse any of the indicated target cells. Although all CTLL expressed the surface markers Thy-1, Lyt-2, Kb, Db and interleukin 2 receptor (IL 2 R), Thy-1 and Lyt-2 markers were drastically reduced and Kb/Db and IL 2 R structures significantly increased on CTLL.4 and CTLL.5 compared to CTLL.1,2,3. In addition, multiple karyotypic alterations including the appearance of metacentric chromosomes were observed in long-term cultured CTLL. Investigations on the expression of the alpha-, beta-, and gamma-chains of the T cell antigen receptor in CTLL.1-5 indicate that all three chains were expressed as mRNA irrespective of whether the lymphocytes expressed their original specificity and/or function. However, distinct beta variable chain genes were used by H-Y-specific CTLL and its long-term culture variants CTLL.2 and CTLL.3 suggesting that the expression of the new specificity was accompanied by the rearrangement of a new beta-chain gene in T effector cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

DNA finger printing by oligonucleotide probes specific for simple repeats.

Interspersed simple repetitive DNA is a convenient genetic marker for analysis of restriction fragment length polymorphisms (RFLPs) because of the numbers and the frequencies of its alleles. Oligonucleotide probes specific for variations of the GATCA simple repeats have been designed and hybridized to a panel of human DNAs digested with various restriction enzymes. Numerous RFLPs were demonstrated in AluI and MboI digested DNA with "pure" GATA oligonucleotides as probes. The optimal length of the probe for RFLP analysis was 20 bases taking into account fragment lengths (1.5-7 kilobases = kb), signal to background ratio, and number of clearly evaluable RFLPs. By using different restriction enzymes individual-specific hybridization patterns ("DNA fingerprints") can be established. Hypervariable simple repeat fragments are stably inherited in a Mendelian fashion. Advantages of this method are discussed.

DNA↗

The organization of the evolutionarily conserved GATA/GACA repeats in the mouse genome.

Simple repeated GATA and GACA sequences which were originally isolated from sex-specific snake satellite DNA have been found subsequently in all eukaryotes studied. The organization of these sequences within the mouse genome was investigated here by using synthetic oligonucleotide probes as a novel tool in comparison with conventional hybridization probes. Southern blot hybridization showed sex-specific patterns with both the (GATA)4 and (GACA)4 oligonucleotide probes, as previously described with conventional probes. The quantitative analysis of two mouse DNA phage libraries and of 25 isolated GATA-positive phage clones revealed intensive interspersion of GATA sequences with GACA, and with other repetitive and single-copy sequences. Ubiquitous interspersion and homogeneous genomic distribution of GATA and GACA sequences were confirmed by hybridization in situ of the oligonucleotide probes to metaphase chromosomes. The lengths of the GATA and GACA stretches were found to vary considerably in the individual phage clones. DNA inserts from 20 phages were assigned to autosomes and sex chromosomes and three genomic fragments were found to be confined to the Y chromosome. The organization of GATA and GACA sequences is discussed in the context of their evolutionary potential and possible conservation mechanisms.

Animals↗

Incidence of squamous cell carcinoma of the head and neck: report of 1,000 cases.

The purpose of this paper is to define the incidence of squamous cell carcinoma (SCC) of the head and neck as seen at the Free University Hospital, Amsterdam, the Netherlands, in the last six years, according to the latest revised classification system of the International Union against Cancer (UICC, 1982). In addition, male to female ratios, relative frequencies at the various sites, age distribution, incidence of second or third primary and the relationship of distant metastases to the nodal metastases and the T-stage of the primary lesion are reported. These incidences are compared with those in other countries and the major differences are discussed.

Adult↗