Biomedical subjects

M Othman

Publications and source records attributed to M Othman.

18 recordsLinked to original sources

PubMed2006

Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics.

We have characterized comprehensive transcript and proteomic profiles of cell lines corresponding to normal breast (MCF10A), noninvasive breast cancer (MCF7) and invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete concordance with microarray results, and also led to the identification of some differentially expressed genes such as lysyl oxidase, copper transporter ATP7A, EphB6, RUNX2 and a variant of RUNX2. The altered transcripts identified by microarray analysis were involved in cell-cell or cell-matrix interaction, Rho signaling, calcium homeostasis and copper-binding/sensitive activities. A set of nine genes that included GPCR11, cadherin 11, annexin A1, vimentin, lactate dehydrogenase B (upregulated in MDA-MB-231) and GREB1, S100A8, amyloid beta precursor protein, claudin 3 and cadherin 1 (downregulated in MDA-MB-231) were sufficient to distinguish MDA-MB-231 from MCF7 cells. The downregulation of a set of transcripts for proteins involved in cell-cell interaction indicated these transcripts as potential markers for invasiveness that can be detected by methylation-specific PCR. The proteomic profiles indicated altered abundance of fewer proteins as compared to transcript profiles. Antisense knockdown of selected transcripts led to inhibition of cell proliferation that was accompanied by altered proteomic profiles. The proteomic profiles of antisense transfectants suggest the involvement of peptidyl-prolyl isomerase, Raf kinase inhibitor and 80 kDa protein kinase C substrate in mediating the inhibition of cell proliferation.

Biomarkers, Tumor↗

PubMed2004

Ultrastructural characteristics of synovial effusion cells in some arthropathies.

OBJECTIVE: To evaluate the range of activation changes of polymorphonuclear leukocytes (PMN) and the ratio of apoptosis and necrosis in synovial effusions of patients with various arthropathies, and to reveal possible correlations with clinical variants of joint inflammation. METHODS: Synovial effusions were aspirated from the knee joints of patients with rheumatoid arthritis (RA, 28 cases), and seronegative spondyloarthritides (SSA): Reiter's disease (RD, 9 cases), peripheral form of the ankylosing spondyloarthritis (6 cases) and psoriatic arthritis (6 cases); and primary osteoarthritis (OA, 9 cases). Cytospin preparations were processed for transmission electron microscopy and assessed for the incidence of apoptosis, necrosis, and cytophagocytic cells (CPC) in the synovial fluid (SF). The range of activation changes of the neutrophil granulocytes, the dominating cell population in the arthritic SF, was evaluated. RESULTS: In all arthropathies under investigation most of the synovial effusion cells had intact ultrastructure with a certain amount of apoptotic cells dominating over the cells with signs of necrosis, and a few CPC. The highest rate of apoptosis was discovered in the synovial effusions of patients with RA, the lowest in those with OA, while the rate of CPC among the inflammatory joint diseases was the lowest in RA. In RA the current disease activity correlated with the incidence of apoptotic cells and CPC, while the clinical stage was related only to the CPC rate. These data suggest that in RA, despite exposure to the anti-apoptotic signals, apoptosis of the synovial effusion PMN is maintained at a significantly higher level than in non-rheumatoid arthropathies, both inflammatory (SSA) and degenerative (OA), providing elimination of the neutrophils accumulating in the joint cavity and thus stimulating resolution of the joint inflammation.

Adolescent↗

PubMed2000

Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma.

PURPOSE: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC). METHODS: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites. RESULTS: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%). CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed.

Adolescent↗

PubMed1999

Humoral response of Meriones libycus to experimental infection with Leishmania major.

The humoral responses of laboratory-reared jirds (Meriones libycus) to inoculation with various doses of Leishmania major were determined. The animals were inoculated intradermally with 10(2), 10(3), 10(5) or 10(7) promastigotes of a strain of L. major originally isolated from a Jordanian patient. The jirds were then bled at various intervals throughout the 26 weeks of the study, and the sera checked, by IFAT, for antibodies to homologous parasites. There were no detectable humoral responses in the animals inoculated with 10(2) promastigotes each or in parasite-free controls but a positive response was apparent in each of the other jirds. The animals given 10(3) promastigotes each required 3 months to become IFAT-positive whereas those given 10(5) and 10(7) parasites only needed 4 and 2 weeks, respectively. More than 50% of the animals inoculated with 10(3) parasites each developed strongly positive sera 2 months post-infection, whereas > 50% of the animals inoculated with 10(5) or 10(7) parasites each had strongly or very strongly positive sera 4 and 2 weeks post-inoculation, respectively. The data indicate that, in M. libycus inoculated with L. major, the time required for the humoral response to develop and its intensity are both dose-related.

Animals↗

PubMed1997

Juvenile glaucoma linked to the GLC1A gene on chromosome 1q in a Panamanian family.

PURPOSE: To characterize clinically and genetically autosomal dominant juvenile-onset primary open-angle glaucoma in a Panamanian family. METHODS: Twenty members of a six-generation family underwent ophthalmologic examination and genetic screening with markers near the GLC1A gene on chromosome 1q. RESULTS: Linkage analysis disclosed evidence linking primary open-angle glaucoma in this family to the GLC1A gene on chromosome 1q, with a maximum lod score of 3.75 for marker D1S431 at an estimated recombination fraction of 0.00. CONCLUSIONS: This is the first report of a Panamanian family in which primary open-angle glaucoma is linked to the GLC1A gene on chromosome 1q.

Adult↗

PubMed1997

Human body model response to mechanical impulse.

Despite our understanding of the importance of falling, previous studies have ignored the effects of falls from standing height. In this article, lumped parameter linear and nonlinear models of a standing human have been used to simulate the impact response of the body segments due to inputs at the shoes. The acceleration transfer and frequency response were determined. The effect of nonlinear damping was simulated. Nonlinear effects were found to be most significant when the input amplitude increases. Frequency response attenuation was significant, resulting in almost a shift in the magnitude plots in the range (0.1-100 Hz) of frequency. When the input amplitude was reduced, the nonlinear effects became apparent only in the medium frequency range. In the case simulating a human subject exposed to impulse at the foot, a large amount of energy is dissipated in the joints due to the friction resulting in a joint disorder. This is most significant at the medium frequency range that is expected to be induced by a running human subject.

Biomechanical Phenomena↗

PubMed1996

Juvenile glaucoma linked to GLCIA in a Panamanian family.

PURPOSE: To carry out clinical and genetic characterization of juvenile-onset primary open-angle glaucoma (POAG) inherited as an autosomal dominant trait in a Panamanian family. METHODS: Twenty-two members of a six-generation Panamanian family underwent an ophthalmologic evaluation. Blood samples were collected from 20 of these individuals for preparation of DNA for use in screening of microsatellite repeat genetic markers via polymerase chain reaction. RESULTS: Eleven living family members covering 4 generations were diagnosed as affected with open-angle glaucoma of primarily juvenile onset. Four of 6 other at-risk individuals examined and enrolled were characterized as unaffected and two as indeterminate. Two additional individuals were not included in this study because they were too young to characterize or to provide a blood sample. Three spouses of affected family members were also examined and found not to have glaucoma. Of clinical importance was the finding of markedly elevated intraocular pressure (IOP) in 2 affected brothers, both of whom were advised to have urgent filtration surgery; the finding of elevated IOP in the only seeing eye of the mother of these brothers, causing us to advise her to pursue more aggressive treatment; and the finding of early signs of glaucoma in a previously undiagnosed 9-year-old family member. Linkage analysis using selected microsatellite repeat markers in the 1q21-q31 region revealed strong evidence for linkage to the GLC1A gene with a maximum lod score of 3.75 for marker D1S431 at a recombination fraction of 0.00. CONCLUSIONS: The most likely interpretation of our data is that a mutation in the GLC1A gene is responsible for juvenile-onset POAG in this Panamanian family, thus expanding the countries of origin where this gene has been found to exist. The numbers of families with GLC1A glaucoma now reported from only a few centers worldwide raise questions about whether this disease may be more common than once thought. Evaluation of treatment histories and clinical outcomes in members of this and other previously reported families indicates that ophthalmologists need to understand the necessity for urgent filtration surgery in most cases of GLC1A glaucoma if vision is to be preserved.

Adult↗

PubMed1995

Scleroderma secondary to silica exposure--a case report.

In recent years there have been many reports of connective tissue diseases especially scleroderma following exposure to silica and silicone. We report a 51-year-old Chinese who developed a scleroderma-like disease and pulmonary silicosis eight years after exposure to silica. To our knowledge, this is the first case to be reported in Malaysia.

Biopsy, Needle↗

PubMed1993

Evolving T cell responses in murine schistosomiasis. Th2 cells mediate secondary granulomatous hypersensitivity and are regulated by CD8+ T cells in vivo.

The dynamics of T cell maturation and regulation were examined during the granulomatous response to Schistosoma mansoni eggs under conditions of primary (PRIM), secondary vigorous (VIG), and secondary immunomodulated (MOD) immunity. The patterns of VIG and MOD GR (GR) formation were established in naive CBA mice by transfer of lymphoid cells from S. mansoni-infected donors at the VIG and MOD stages of infection. Sequential production of IFN, IL-2, and IL-4 was assessed at the GR and in draining lymph nodes (LN) to determine the participation of Th1 (IFN-producing) and Th2 (IL-4/IL-5-producing) cells. The PRIM GR produced IFN in the growth phase (2-16 days) and IL-4 was detected only after lesions were established (16-24 days). The PRIM LN showed coincident production of IFN, IL-2, and IL-4 on day 4 followed by mainly IL-4 and IL-2 production on day 8, consistent with Th2 differentiation via a Th0 precursor. The VIG GR produced high levels of IL-4 in the growth phase (4-8 days) although IFN remained at modest levels. The VIG LN showed increased cytokine levels consistent with an anamnestic response and again the pattern suggested Th2 differentiation from Th0 cells. The MOD mice had abrogated GR IL-4 levels and arrested Th2 differentiation in LN. In vitro mix studies indicated that the impaired cytokine production was not due to direct suppression. The role of Ts cells was next explored by T cell subset depletion. Pan-T cell depletion of VIG cells profoundly abrogated IL-4 production although CD8+ cell depletion augmented GR area by 70% as well as local and regional IL-4 production by 100 to 150%. Similarly, CD8+ cell depletion of MOD cells augmented GR size and IL-4 production but the response was less than corresponding VIG mice, suggesting that Th activity was reduced in MOD mice. Transfer studies indicated that CD8+ cells inhibited Th2 maturation in LN. Thus, the schistosome egg GR demonstrated a Th1-like pattern in the PRIM response followed by a Th2 pattern in the VIG stage and abrogated Th2 activity in the MOD stage. Finally, the phenomenon of "spontaneous modulation" likely represents the cumulative action of CD8+ cells which steadily erode the Th population.

Animals↗

PubMed1990

Transient increase in Ca2+ influx in Saccharomyces cerevisiae in response to glucose: effects of intracellular acidification and cAMP levels.

Influx of 45Ca2+ into Saccharomyces cerevisiae was measured under experimental conditions which enabled measurements of initial rate of transport across the plasma membrane, without interference by the vacuolar Ca2+ transport system. Addition of glucose or glycerol to the cells, after pre-incubation in glucose-free medium for 5 min, caused a rapid, transient increase in 45Ca2+ influx, reaching a peak at 3-5 min after addition of substrate. Ethanol, or glycerol added with antimycin A, had no effect on 45Ca2+ influx. We have shown previously that this increase is not mediated by an effect of the substrates on intracellular ATP levels. Changes in membrane potential accounted for only a part of the glucose-stimulated 45Ca2+ influx. The roles of intracellular acidification and changes in cellular cAMP in mediating the effects of glucose on 45Ca2+ influx were examined. After a short preincubation in glucose-free medium addition of glucose caused a decrease in the intracellular pH, [pH]i, which reached a minimum value after 3 min. A transient increase in the cellular cAMP level was also observed. Addition of glycerol also caused intracellular acidification, but ethanol or glycerol added with antimycin A had no effect on [pH]i. Artificial intracellular acidification induced by exposure to isobutyric acid or to CCCP caused a transient rise in Ca2+ influx but the extent of the increase was smaller than that caused by glucose, and the time-course was different. We conclude that intracellular acidification may be responsible for part of the glucose stimulation of Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimycin A↗

PubMed1990

Activation of Ca2+ influx by metabolic substrates in Saccharomyces cerevisiae: role of membrane potential and cellular ATP levels.

Influx of Ca2+ into cells of Saccharomyces cerevisiae was measured under non-steady-state conditions, which enable measurements of the initial rate of transport across plasma membranes without interference by the vacuolar Ca2+ transport system. Removal of glucose from the incubation medium led to inactivation of Ca2+ influx within 5 min. Readdition of glucose led to a transient increase in the rate of Ca2+ transport, reaching a peak after 3-5 min. A second increase was observed 60-80 min later. To examine whether the first transient activation of Ca2+ influx by glucose was mediated by membrane hyperpolarization, influx of 45Ca2+ was measured in the presence and absence of metabolic substrates (glucose, glycerol, and glucose plus antimycin A) in cells hyperpolarized to different values of membrane potential (delta psi). Logarithms of the rate of Ca2+ influx were plotted against values of delta psi. Two different slopes were obtained, depending upon whether the metabolic substrate was present or absent. Ca2+ influx in the presence of the metabolic substrates was always higher than expected by their effect on delta psi. Glycerol plus antimycin A did not affect Ca2+ influx. It was concluded that metabolized substrates activate Ca2+ influx not only by effects on delta psi but also by additional mechanism(s). Since no simple correlation between Ca2+ influx and intracellular ATP levels was observed, it was concluded that ATP levels do not affect the initial rates of Ca2+ transport across the plasma membrane of S. cerevisiae.

Adenosine Triphosphate↗

PubMed1990

Comparison of methods in the detection of enterotoxigenic Escherichia coli in a Malaysian laboratory.

The prevalence of Enterotoxigenic Escherichia coli (ETEC) in 433 stool samples from diarrhoeal cases of all ages was studied using two commercially available test kits for the detection of heat labile toxin (LT) and the infant mouse assay for the heat stable toxin (ST). 16 samples (3.7%) were positive for ETEC, of which nine were producing ST alone, six LT alone and only one was producing both LT and ST. Although the percentage of isolation rate was low, its occurrence was almost as common as the Shigella spp and Salmonella spp in the same study. Of the two test kits examined, the Phadebact ETEC-LT Test 50 (Pharmacia Diagnostics, Uppsala, Sweden) was found to be more suitable for use in a routine diagnostic laboratory. Ten out of 12 (83%) of the strains tested were resistant to one or more antibiotics.

Adolescent↗

PubMed1989

Course of infection and humoral response to Leishmania major in inbred Meriones unguiculatus.

Numerous species of Meriones have been incriminated as natural reservoir hosts of Leishmania major in Mongolia, Soviet Asia, Afghanistan, the Middle East, and North Africa. However, little is known about the immunological response or course of infection in these small rodents. In this study, 40 commercially obtained inbred Meriones unguiculatus were divided into equal groups and injected in the right hind footpad with various doses of L. major promastigotes or with medium only. At regular intervals, blood was collected from the animals for subsequent evaluation of the kinetics of anti-L. major serum antibody production. Footpad lesions were measured periodically for 13 wk, beginning just before infection. The humoral response to infection and the course and severity of disease were dose related. However, metastasis lymph nodes, liver, spleen, and secondary cutaneous sites occurred at each of the doses tested.

Animals↗

PubMedDate not supplied

Immunomagnetic separation of adult human olfactory neural progenitors.

Olfactory neuroepithelium (ONe) has lifelong regenerative capacity owing to the presence of mitotically active progenitors. The accessibility of ONe makes it a unique source of progenitors for cell replacement strategies in the CNS. We have established lines of neurosphere forming cells (NSFCs) from adult postmortem ONe and patients undergoing nasal sinus surgery by endoscopic biopsy. These heterogeneous lines are composed primarily of an immature neuronally restricted and a small glial restricted subpopulation. More homogeneous subpopulations of the NSFCs are essential for detailed study of factors influencing their lineage restriction. Immunomagnetic bead separation using an antibody against tyrosine kinase (Trk) receptors (Trk-pan, which recognizes Trk-A, B, C) resulted in viable, enriched positive and negative subpopulations that could be analyzed immunocytochemically. The positive cells remained positive for the first week after which the number of Trk-pan expressing cells decreased. The negative subpopulation began to express Trk-pan immunoreactivity after five days in vitro. Both subpopulations reverted to the heterogeneous composition after two weeks. Furthermore, most NSFCs were positive for Trk-B, a few for Trk-A, while no reactivity was observed for Trk-C. Because NSFCs produce brain derived neurotrophic factor (BDNF) and express Trk B, the specific receptor for BDNF, it is likely that population dynamics are under a paracrine and/or autocrine regulatory mechanism. Lineage restriction analysis demonstrated that the isolated subpopulation had a restriction potential equivalent to the original heterogeneous population. These studies characterize further the NSFCs and support the future potential therapeutic use of ONe-derived progenitors for CNS injury and neurodegenerative disorders.

Adult↗

PubMedDate not supplied

Clonal analysis of adult human olfactory neurosphere forming cells.

Olfactory neuroepithelium (ONe) is unique because it contains progenitor cells capable of mitotic division that replace damaged or lost neurons throughout life. We isolated populations of ONe progenitors from adult cadavers and patients undergoing nasal sinus surgery that were heterogeneous and consisted of neuronal and glial progenitors. Progenitor lines have been obtained from these cultures that continue to divide and form nestin positive neurospheres. In the present study, we used clonal and population analyses to probe the self-renewal and multipotency of the neurosphere forming cells (NSFCs). NSFCs plated at the single cell level produced additional neurospheres; dissociation of these spheres resulted in mitotically active cells that continued to divide and produce spheres as long as they were subcultured. The mitotic activity of clonal NSFCs was assessed using bromodeoxyuridine (BrdU) incorporation. Lineage restriction of the clonal cultures was determined using a variety of antibodies that were characteristic of different levels of neuronal commitment: ss-tubulin isotype III, neural cell adhesion molecule (NCAM) and microtubule associated protein (MAP2), or glial restriction: astrocytes, glial fibrillary acidic protein (GFAP); and oligodendrocytes, galactocerebroside (GalC). Furthermore, nestin expression, a marker indicative of progenitor nature, decreased in defined medium compared to serum-containing medium. Therefore, adult human ONe-derived neural progenitors retain their capacity for self-renewal, can be clonally expanded, and offer multipotent lineage restriction. Therefore, they are a unique source of progenitors for future cell replacement strategies in the treatment of neurotrauma and neurodegenerative diseases.

Adult↗

PubMedDate not supplied

Assessment of the delayed neurotoxicity of tributyl phosphate, tributoxyethyl phosphate, and dibutylphenyl phosphate.

There industrial organophosphorus compounds were tested for their ability to cause organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the adult hen. The compounds tested were tributyl phosphate (TBP), tributoxyethyl phosphate (TBEP), and dibutylphenyl phosphate (DBPP). The acute oral LD50 of TBP and DBPP were estimated to be 1,863 and 1,500 mg/kg, respectively, and the dose equal to the LD50 was used as a test dose. The acute oral LD50 of TBEP was greater than 5,000 mg/kg and 5,000 mg/kg was used as a test dose. An oral dose of 750 mg tri-o-cresyl phosphate (TOCP) was used as a positive control. For the acute delayed neurotoxicity test, hens were given two test doses of the test materials 21 days apart and killed 21 days after the second dose. None of the hens given TBP, TBEP, or DBPP exhibited nerve damage or clinical signs which distinguished them from untreated control animals. A single dose of TOCP resulted in paralysis and a histopathological profile typical of a distal neuropathy. For the assay of the inhibition of esterases, hens were killed 24 hours after a single dose equal to the greater of either the LD50 or 5000 mg/kg. TOCP administration resulted in over 90% inhibition of brain neurotoxic esterase (NTE), but none of the other three compounds inhibited NTE to an extent (greater than 70%) which would be expected to result in OPIDN. Administration of TOCP, TBEP, or DBPP resulted in approximately a 70% decrease in plasma butyrylcholinesterase (BuChE) activity. TBP caused a 2-3 fold increase in BuChE activity. TBEP administration resulted in about 45% inhibition of acetycholinesterase (AChE) in brain. These results indicate that TBP, TBEP, and DBPP are all unlikely to cause OPIDN with any single sublethal dose.

Animals↗

PubMedDate not supplied

ECG response of the human body subjected to vibrations.

In this paper, the ECG response of the human body subjected to vibrations is investigated. Measurements relied on recording the ECG and then computing the normalized difference of the ECG power spectrum density. Ten subjects aged 20-22 years old were exposed for 15 min to vertical vibrations in the frequency range 5-30 Hz. Results show either depression or elevation of the ST segment indicating heart muscle fatigue. The power spectrum density normalized difference also shows that the maximum difference takes place at 8 Hz vibrations frequency which is thought to be around the resonance frequency of the heart.

Adult↗

PubMedDate not supplied

Heart response to horizontal impulse.

Lumped body parameters linear and nonlinear models have been developed and used for the analysis of the response of the heart in a seated human body due to impulsive horizontal inputs at various body segments. The acceleration transfer magnitude and phase due to impulsive inputs at various body segments are reported. Time histories of the heart acceleration transfer were obtained for both linear and nonlinear models. The results indicate that the largest acceleration transfer occurs at 2-3 Hz frequency. Inputs at the upper body segments excite a second peak and in the acceleration transfer at 10-12 Hz. The nonlinear model shows large attenuation at the high frequency range (larger than 10 Hz) and less attenuation at the 1-5 Hz frequency range.

Abdomen↗