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Biomedical subjects

S A Ali

Publications and source records attributed to S A Ali.

At least 55 records · Page 3Linked to original sources

Collagen type IV promotes the differentiation of neuronal progenitors and inhibits astroglial differentiation in cortical cell cultures.

In an effort to elucidate the interactions between cells in the developing cortex and their microenvironment, we have employed dissociated cell cultures and immunocytochemistry to analyze the effect of collagen type IV (COL) on the proliferation and differentiation of rat cortical progenitor cells during the period of corticogenesis. COL, present in the proliferative zones throughout the period of neurogenesis, belongs to a group of macromolecular proteins that make up a considerable portion of the extracellular matrix (ECM). We have shown that this ECM molecule inhibits cell proliferation and glial cell differentiation while promoting neuronal differentiation. We have also demonstrated that COL, when applied to the cultures with basic fibroblast growth factor (bFGF), induces glial cell differentiation while continuing to promote neuronal differentiation. These results indicate that cortical progenitor cells respond differentially to local environmental signals, and that components of the ECM are involved in the regulation of corticogenesis.

Animals↗

Interaction of Doxorubicin with phospholipid monolayer and liposomes.

The effect of Doxorubicin which is (an anthracycline antibiotic with a broad spectrum of antitumor activity) on the monolayer and bilayer in the form of large Multilamellar Vesicles (MLV's) of Dipalmitoyl phosphatidylcholine (DPPC) were studied by means of monolayer techniques (surface pressure, penetration kinetics, and association constant) and light scattering technique. The monolayer technique showed that addition of DXR to a lipid film composed of (DPPC/CHOL/PEG-PE) at a molar ratio of (100:0:0) produced a less condensed Monolayer. In the (pie-A) curves, DXR induced shift towards larger area/molecule, where the area/molecule was shifted from 61 to 89 A2, and 116 A2 in the presence of 20 and 40 nM DXR, respectively. The three curves collapsed at a pressure pi = 45 mN/m. In penetration kinetics experiment (delta pi-t), the change in pressure with time was 8 and 14 mN/m for a DXR concentration of 20 and 40 nM, respectively, and the increase in surface pressure presented a plateau over a period of 30 min. The measured association constant (K) was found to be 5 x 10(5)/M. In the light scattering experiment, there was a shift of the transition temperature (Tm) of (MLV's) of the same composition of the monolayer towards a smaller value from 40.5 degrees to 34.5 degrees C. Incorporation of CHOL and PEG-PE as DPPC/CHOL/PEG-PE at a molar ratio of (100:20:0), (100:20:4) and (100:20:4) greatly counteracted the effect of DXR and made the lipid membrane more condense and rigid. Moreover, the penetration of DXR into the membrane was greatly reduced. There was a very small shift for the (pi-A) and (delta pi-t) curves, and the association constant of the drug for these different lipid compositions was greatly reduced down to 2.5 x 10(5)/M and the transition temperature (Tm) was increased up to (42.5 degrees C) in the presence of 40 nM DXR. Our results suggest that DXR has a great effect on the phospholipid membrane, and that addition of CHOL or PEG-PE to the phospholipid membrane causes stabilization for the membrane, and reduces the interaction with Doxorubicin.

1,2-Dipalmitoylphosphatidylcholine↗

Histamine receptors in the skin melanophores of Indian bullfrog Rana tigerina.

Histamine and 2-methyl histamine caused dose-dependent aggregation of the integumental melanophores of Rana tigerina both in vitro and in vivo. The aggregating effects were antagonised by mepyramine and metiamide, specific H1 and H2 receptor blockers, respectively. Compound 48/80 and EDTA augmented the melanin-aggregating effects of exogenously applied histamine and 2-methyl histamine in in vivo experiments. 4-Methyl histamine, a specific H2 receptor agonist, dispersed the frog melanophores in in vitro studies, the dispersing effects were blocked by metiamide.

Animals↗

Purification and primary structure of low molecular mass peptides from scorpion (Buthus sindicus) venom.

The primary structures of four low molecular mass peptides (Bs 6, 8, 10 and 14) from scorpion Buthus sindicus were elucidated via combination of Edman degradation and matrix-assisted laser desorption ionization mass spectrometry. Bs 8 and 14 are cysteine-rich, thermostable peptides composed of 35-36 residues with molecular weights of 3.7 and 3.4 kDa, respectively. These peptides show close sequence homologies (55-78%) with other scorpion chlorotoxin-like short-chain neurotoxins (SCNs) containing four intramolecular disulfide bridges. Despite the sequence variation between these two peptides (37% heterogeneity) their general structural organization is very similar as shown by their clearly related circular dichroism spectra. Furthermore, Bs6 is a minor component, composed of 38 residues (4.1 kDa) containing six half-cystine residues and having close sequence identities (40-80%) with charybdotoxin-like SCNs containing three disulfide bridges. The non-cysteinic, bacic and thermolabile Bs10 is composed of 34 amino acid residues (3.7 kDa), and belongs to a new class of peptides, with no sequence resemblance to any other so far reported sequence isolated from scorpions. Surprisingly, Bs10 shows some limited sequence analogy with oocyte zinc finger proteins. Results of these studies are discussed with respect to their structural similarities within the scorpion LCNs, SCNs and other biologically active peptides.

Animals↗

Fibronectin is chemotactic for CT 26 colon carcinoma cells: sub-lines selected for increased chemotaxis to fibronectin display decreased tumorigenicity and lung colonization.

CT 26 murine colon carcinoma cells demonstrated directional migration (chemotaxis) in response to fibronectin (FN). Sub-lines were derived by positive and negative selection to FN across Transwell filters of 8 microm pore size. The FL6 sub-line (positively selected) demonstrated a significantly increased chemotactic response (P<0.01) to FN compared with parental CT 26 cells, while the FU7 sub-line (negatively selected) showed a reduced chemotactic response to FN (P<0.01). Comparable levels of alpha4, alpha5, alphav and beta1 integrins, which mediate FN attachment, were expressed on positively and negatively selected sub-lines and parental CT 26 cells. Activation of integrins with Mn2+ suggested that the integrins expressed on FL6 cells were in the fully activated state; in contrast FU7 cells displayed only partially activated integrins. Cell attachment and integrin activation status of the sub-lines correlated with their chemotactic response to FN. In vivo FL6 cells showed a significantly reduced tumour growth rate s.c. and a reduction in the number of lung colonies formed following i.v. injection compared with parental CT 26 and FU7 cells. In contrast FU7 cells displayed a significant increase in s.c. tumour growth and the number of lung colonies when compared with the parental line and FL6 sub-line. The results indicate that interaction between integrin receptors expressed on cancer cells and FN plays a central role in the chemotactic response of CT 26 colon carcinoma cells, and that in this model cells selected for chemotaxis to FN displayed a reduced malignant potential.

Adenocarcinoma↗

Spinal-cerebrospinal fluid leak demonstrated by radiopharmaceutical cisternography.

Cerebrospinal fluid (CSF) leaks are known to occur under several conditions: lumbar puncture performed for contrast myelography, spinal surgery, spinal stab wounds, fracture of the thoracic spine, inadvertent spinal puncture during epidural anesthesia, traumatic lumbar meningocele, and bronchopleural subarachnoid fistula due to bronchogenic carcinoma. Spontaneous spinal leaks are uncommonly encountered in neurosurgical practice, but they are increasingly recognized as a cause of spontaneous intracranial hypotension. Most CSF leaks are located at the cervicothoracic junction or in the thoracic spine. The disease is often self-limiting. A CSF leak can be detected directly by accumulation of radioactivity outside the subarachnoid space or suggested indirectly by the rapid disappearance of tracer from the subarachnoid space and early appearance in the urinary bladder. In this paper we present two unusual cases of CSF leak identified by radiopharmaceutical cisternogram.

Adult↗

Sarcoid: an unusual mimicker of classic pulmonary embolus.

A patient had both the clinical presentations and the ventilation-perfusion scan that simulated pulmonary embolism so closely that anticoagulant therapy was administered. Computed tomography of the chest and Ga-67 citrate scintigraphy identified hilar adenopathy due to sarcoidosis as the cause of a ventilation-perfusion mismatch.

Adult↗

A semisynthetic fetal calf serum-free liquid medium for in vitro cultivation of Leishmania promastigotes.

A semisynthetic, autoclavable, liquid medium that does not require inclusion of fetal calf serum (FCS) for the successful cultivation of Leishmania promastigotes in vitro is described. The parasites were grown in commercially available medium 199 supplemented with 10% FCS and 2% mammalian urine and the growth was compared with the same medium without FCS. The growth of the parasites in the semidefined medium without FCS was found to be as good as or slightly better that with medium 199 supplemented with FCS.

Animals↗

Population based data on urinary excretion of various metabolites in children of north western region of Pakistan.

Population based data on urinary excretion of various metabolites of pathological importance, Calcium, Magnesium, Sodium, Potassium, Oxalates, Citrates, Phosphates, Uric acid and urea have been collected from around three hundred children of the Quetta valley. The body weight was in the range of 11-50 kg and the age was in between 4-16 years. The urine excretion average was 987.5 +/- 452.5 ml per 24 hours. There was 11.5% incidence of hypercalciuria, 8.5% incidence of hyperuricosuria, 2.0% hyperphosphaturia, 2.5% hypomagnesuria, 3.5% hypocitraturia, 6.5% hypernatriuria, 43.5% hypokaliurea and 2.1% hyperoxaluria. Urea excretion average was 23.11 +/- 14.99 g per 24 hours. The study provided the basis for childhood reference pattern in urinary excretion of compounds related to various pathological conditions, in particular stone formation in this region.

Adolescent↗

Physician compliance with national tuberculosis treatment guidelines: a university hospital study.

SETTING: The Aga Khan University Hospital, in Karachi, Pakistan, is a 650-bed university teaching hospital. OBJECTIVES: There is little data from Pakistan on the awareness and application of the World Health Organization (WHO)'s tuberculosis treatment guidelines among physicians. This study evaluates physician compliance with these guidelines. DESIGN: A questionnaire to measure physician compliance was developed, pilot tested and standardised. Case records of all patients hospitalized with tuberculosis were reviewed (January-December 1995, n = 229), and were classified into WHO Category 1 (n = 191), Category 2 (n = 9) and Category 3 (n = 29). RESULTS: A total of 53 (23%) patients had a diagnostic bacteriological sputum smear examination, of which 38% were smear positive and 47% culture positive. Of 25 cerebrospinal fluid cultures 12% were positive. No sputum smear tests were conducted during treatment. Of 58 patients in Category 1 who completed therapy 74% received a 2-month intensive phase consisting of HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) (n = 43), while 41% received a 6 month continuation phase with HE (n = 24). Over 70% patients were lost to follow up, more than half of these during the intensive phase. CONCLUSION: Our study reflects poor awareness of the WHO guidelines and low compliance among physicians, and a high loss to follow-up. Efforts are needed to create physician awareness about the WHO guidelines and their use. This study can be used to assess the effectiveness of any future physician education and to identify areas of weakness in health care.

Antitubercular Agents↗

Chemokines induce migrational responses in human breast carcinoma cell lines.

Chemokines have been shown to chemoattract and activate different leukocyte populations. Here we report the in vitro effect of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation, normal T-cells, expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), interferon inducible protein-10 (IP-10), neutrophil-activating peptide-2 (NAP-2), growth-related protein (GRO)-alpha and GRO-gamma, on the migration of 3 human breast carcinoma cell lines, MCF-7, T47D and ZR-75-1, using a microchemotaxis chamber to assess migration across fibronectin-coated polycarbonate membranes. MCF-7 cells responded chemotactically to all chemokines tested in a pattern which was dose and time dependent, although responses to the different chemokines were variable. ZR-75-1 responded to MIP-1beta and GRO-alpha, giving maximum migration indices of 3.7 and 5.3, respectively, and exhibited a migratory response to MIP-1alpha, IL-8 and MCP-1 although to a lower degree. T47D was unresponsive to the chemokines tested, but both MCF-7 and T47D cells bound radiolabelled ligands with binding constants (Kd) ranging from 0.6 to 2.2 nM and 0.6 to 2.1 nM, respectively. The specificity of the chemotactic response of MCF-7 to MIP-1alpha and MIP-1beta was confirmed using chemokine-specific neutralising antibodies and heat denaturation, and was demonstrated to involve G protein and cyclic AMP signalling pathways. MIP-1beta and MIP-1alpha were shown to induce changes in the organisation of the actin cytoskeleton and the level of F-actin in MCF-7 cells, as determined using flow cytometric analysis and confocal microscopy. Our results show that breast carcinoma cells can respond to chemokines, and suggests a potential role for these molecules in the process of tumour cell migration, invasion and metastasis.

Actins↗

Migration responses of human monocytic cell lines to alpha- and beta-chemokines.

The beta-chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1alpha), MIP-1beta and regulated on activation, normal T cells, expressed and secreted (RANTES) induced the in vitro migration of the monocytic cell line MonoMac-6. MCP-1 exhibits the most potent chemotactic effect on this cell line while MIP-1alpha, RANTES and to a lesser extent MIP-1beta were more moderate inducers of cell migration. MonoMac-6 migration in response to chemokines was shown to be a chemotactic and not a chemokinetic response, which was inhibited by pertussis and cholera toxins suggesting a role for G proteins in chemokine receptor-mediated signalling in these cells; chemotaxis of MonoMac-6 cells in response to MCP-1 was abrogated by the addition of anti-MCP-1 antibody. The response of MonoMac-6 cells to the alpha-chemokines IL-8, IP-10, growth-related peptide (Gro) alpha and MIP-2beta was substantially weaker than to the beta-chemokines. MCP-1 caused an alteration in cellular morphology by increasing ruffling at the cell membrane and the number of cells exhibiting extended pseudopodia. The chemotactic response of MonoMac-6 cells to beta-chemokines was compared with less well-differentiated myelomonocytic cell lines. THP-1 showed a similar, but weaker response to the beta-chemokines while both HL60 and U937 failed to respond to any member of this subfamily when tested under the same conditions. These results suggest that the differentiation status of cells of monocytic lineage may affect their response to beta-chemokines.

Cell Line↗

Three-phase Tc-99m labeled RBC scintigraphy of a splenic hemangioma.

A 46-year-old man presented with right upper quadrant pain with a clinical suspicion of cholelithiasis and was referred for an abdominal ultrasound (US). On US evaluation, the liver and gallbladder were normal. Incidentally noted a homogeneous, well demarcated, hyperechoic, 5-cm mass in the inferior portion of the spleen. A subsequent Tc-99m labeled RBC scan showed a 5-cm photopenic area in the inferior portion of the spleen on perfusion and early blood pool images. Subsequent filling in on delayed images with slightly increased uptake relative to surrounding splenic tissue was seen on the final images (85 min). Splenic hemangiomas are rare neoplasms, although they still represent the most common primary neoplasm of the spleen. The incidence of splenic hemangiomas ranges from 0.03-14% in autopsy studies.

Erythrocytes↗

Cytokine modulation of antigen expression in human melanoma cell lines derived from primary and metastatic tumour tissues.

The constitutive and cytokine-mediated expression of MHC class I and II antigens and intercellular adhesion molecule-1 (ICAM-1) was evaluated on eight human melanoma cell lines derived from primary and metastatic malignancies from patients (WM human melanoma series) including three pairs of related cell lines derived from the same individual. The cytokines IL-1 beta, IL-4, IL-6, TNF alpha, TGF beta 2, IFN gamma and IFN alpha were assessed for their ability to modulate the expression of cell surface antigens. MHC class I and class II antigen expression was unregulated by IFN gamma, IFN alpha and/or TNF alpha in cell lines established from primary melanoma. In contrast the cell lines derived from metastatic deposits did not show an increase in expression of MHC antigens in response to these cytokines. Both primary and metastatic WM cell lines were shown to be resistant to spontaneous natural killer cell (NK) activity, but susceptible to effector lymphocytes mediating lymphotine activated killer (LAK) cytotoxicity as a result of activation by IL-2. Although the constitutive and cytokine-induced level of expression of ICAM-1 and MHC antigens varied between paired primary and metastatic cell lines, this did not correlate with susceptibility of the cell line target to NK or LAK cytotoxicity. Whereas the IFNs, TNF alpha, TGF beta 2 and IL-1 beta differentially modulated the expression of ICAM-1 and MHC class I, treatment with IFNs (but not IL-1 beta, TNF alpha or TGF beta 2) resulted in a significant reduction in the sensitivity of the melanoma cells to NK and LAK cytotoxicity. Constitutive ICAM-1 expression was positively correlated with the ability of WM cell lines to colonise the lungs of SCID mice upon i.v. injection. The acquisition of cytokine resistance and inability to demonstrate enhanced cell surface expression may represent an important feature associated with the development of the metastatic phenotype.

Animals↗