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Biomedical subjects

A Saleem

Publications and source records attributed to A Saleem.

86 records · Page 5Linked to original sources

Leukemic transformation in myelodysplastic syndrome: a review.

The literature was reviewed by us for leukemic transformation in the myelodysplastic syndrome (MDS). The factors reviewed included morphology, karyotype, in vitro cell culture, cellular oncogenes, genetic mutations and cell markers. Karyotypic abnormalities appeared to be most commonly associated with leukemic transformation in MDS. These abnormalities include: (1) Chromosomal abnormalities at the time of diagnosis; (2) multiple chromosomal abnormalities, especially in patients previously exposed to cytotoxic drugs, and (3) New chromosomal abnormalities following diagnosis. Leukemic transformation was also associated with non-random chromosomal abnormalities, abnormal localization of immature precursors (ALIP), dysgranulopoiesis and dysmegakaryocytopoiesis, in vitro cell cultures showing high cluster/colony ratio, and N-ras oncogene mutation and activation. However, karyotypic analysis at presentation and during the course of the disease appears to be the best predictor for leukemic transformation in patients with MDS.

Cell Transformation, Neoplastic↗

Acute myelofibrosis--a leukemia of pluripotent stem cell. A report of three cases and review of the literature.

The histogenesis of blasts in acute myelofibrosis is generally regarded to be of megakaryocytic origin. Three case reports are presented and 19 other reported cases were reviewed from the literature where the cells of origin appear to be myeloblasts, myelomonoblasts, lymphoblasts, or undifferentiated blasts. It is therefore postulated that acute myelofibrosis is a hemopoietic stem cell disorder, and acute megakaryocytic leukemia (FAB-M7) represents one subset of the disorder.

Aged↗

Immunosuppressive mechanisms in pure red cell aplasia--a review.

Pure red cell aplasia (PRCA) has been associated with a variety of clinical disorders, and various autoimmune mechanisms have been described to account for the red cell suppression. Primary PRCA occurs via both humoral and cell mediated mechanisms. Recent evidence using gene rearrangement studies indicates PRCA with T-lymphocytosis is a clonal chronic T cell lymphoproliferative disorder in which the T cells suppress erythropoiesis. Called T cell lymphocytosis and cytopenia (TCLC), this disorder has unique features, such as frequent rheumatoid arthritis (RA) and neutropenia. A subset of this disorder with natural killer (NK) like cells also exists, though direct NK cell suppression has not been proven. In secondary PRCA, both humoral and cellular suppression of erythropoiesis have also been described, except in chronic lymphocytic leukemia (CLL) where T cell suppression primarily accounts for the red cell aplasia. A role for the cell-adherent layer of the bone marrow, including macrophages, has also been demonstrated.

Humans↗

The congo red stain revisited.

The Congo red stain has undergone several modifications since it was first used by Bennhold in 1922 in order to increase the specificity for staining amyloid. Most of the laboratories in the United States use the method of Puchtler which uses alkaline Congo red solution. Some of the variables associated with the procedure were investigated by us. Our results showed the following: (1) amyloid showed green birefringence at all levels between 4 to 12 mu thick sections with better visualization of small deposits with increased thickness. Best results were obtained with 8 mu thick sections; (2) omission of the pretreatment with alkaline alcoholic solution of sodium chloride (NaCl) did not affect the sensitivity of the method; (3) the use of polar mounting media had no effect on amyloid and collagen birefringence; (4) 50 percent saturation of the Congo red staining solution with NaCl caused strong staining of collagen, elastic fibers and eosinophilic granules. In addition, collagen showed green birefringence and dichroism and its differentiation from amyloid became difficult; and (5) using the staining solution fully saturated with NaCl, no positive staining was seen with tissues other than amyloid. Collagen and elastic fibers showed red fluorescence which was of less intensity than amyloid. It is our conclusion that the method of Puchtler for detecting amyloid gives better results if the staining solution is fully saturated with NaCl. The pretreatment step may be deleted without compromising the quality of staining. Improved staining of amyloid enhances the specificity of green birefringence, dichroism, and red fluorescence.

Amyloid↗

MR imaging of hyperacute intracranial hemorrhage in the cat.

Hyperacute intracerebral hematomas were successfully created in five cats by injecting a prepared blood sample in which the oxygen (O2) saturation ranged from 0-80%. T1- and T2-weighted spin-echo sequences and T2-weighted gradient refocused scans were obtained 2.5-10 hr after injection on a 1.5-T imaging system. Detailed histology or electron microscopy was performed on each brain to confirm the presence of intact red blood cells in a retracted clot matrix. Areas of the hematoma were hypointense relative to brain in all five cats on the gradient refocused scans. The hematoma was isointense relative to brain on the T1- and T2-weighted spin-echo scans in all cats except one, which suffered a seizure/respiratory arrest and died during the scanning procedure. Portions of the hematoma in this animal had a hypointense T2-weighted signal and a hyperintense T1-weighted signal, which corresponded to the predicted MR properties of intracellular methemoglobin. We hypothesize that acute (less than 10 hr old) hematomas that contain virtually 100% intracellular deoxyhemoglobin may not appear hypointense relative to brain on T2-weighted scan sequences at 1.5 T unless surrounding tissue hypoxia and/or anoxia promote additional changes, one of which may be the formation of intracellular methemoglobin.

Acute Disease↗

Effect of clot formation and retraction on spin-echo MR images of blood: an in vitro study.

Phantoms were constructed that contained red blood cell (RBC)-free clots in varying stages of clot retraction. MR images of these samples were compared with those of retracted whole venous blood clots and a fresh rat brain standard. Images were obtained at 0.3 T, 0.5 T, 1.0 T, 1.5 T, and 2.4 T with T1-, spin-density- and T2-weighted spin-echo pulse sequences. The presence or absence of venous blood cells in the clot caused only minor differences in T2- and spin-density-weighted images of the clots at or below 1.5 T. On T2-weighted scans, the retraction of the RBC-free clot resulted in a progressive decrease in signal intensity at 2.4 T. Fully retracted RBC-free clots were markedly hypointense relative to serum and ranged from slightly hyperintense to isointense with brain and venous clots at 0.5-1.5 T. There were no striking concomitant signal intensity changes on the spin-density- or T1-weighted scans, which could have caused the changes seen on the T2-weighted images of the clots. Our results indicate that the physical basis of these MR effects in the RBC-free clots is the concentration of plasma protein. The combined concentration of plasma protein and the tightly packed RBC proteins in the venous clots causes the strikingly similar MR appearance of venous and RBC-free clots on clinical images. These results do not demonstrate the presence of the previously postulated selective T2 relaxation of intracellular paramagnetic deoxyhemoglobin in these in vitro venous clots.

Animals↗

Prekallikrein (Fletcher factor) deficiency.

One new case and 29 reported cases of hereditary prekallikrein (Fletcher factor) deficiency are reviewed. Abnormalities in the coagulation, fibrinolytic, complement, and kinin systems are described. These cases are discovered incidentally by prolonged partial thromboplastin times (PTTs) which correct with extended incubation in the presence of a contact activator. Prekallikrein levels are less than two percent of normal levels. In general, the remainder of the coagulation profile is normal, and no bleeding diathesis is present. Most patients are black and the incidence of consanguinity is increased. The disease is transmitted in an autosomal recessive manner. Acquired Fletcher factor disease is a moderate prekallikrein deficiency present in many common disease states. Its clinical significance is largely unknown. Both acquired and hereditary forms may rarely predispose to thrombotic phenomena.

Adult↗

Effect of profound hypothermia on leukocytes and platelets.

Seventeen patients who underwent aortic arch replacement were subjected to profound hypothermia and circulatory arrest. At maximum cooling, platelet count dropped from 184 +/- 122 to 37 +/- 30 thousand per microliter, and the total leukocytic count fell from 6.27 +/- 4.0 to 1.47 +/- 0.6 thousand per microliter. The thrombocytopenia was partially reversed with rewarming. The total white cell count consistently returned to precooling values or higher (10.5 +/- 4.0). The mechanism for this cold induced phenomenon is not well understood.

Aorta, Thoracic↗

Heparin monitoring during cardiopulmonary bypass.

Three procedures have been compared for monitoring heparin in patients undergoing cardiopulmonary bypass: (1) activated clotting time (ACT) (2) protamine titration, and (3) fluorometric substrate assay. The ACT monitors the degree of anticoagulation. It is easy to perform and is relatively inexpensive, however, it does not correlate well with heparin levels and may not accurately predict the protamine dose for neutralization of heparin at the completion of bypass. A protamine titration assay or an assay using a thrombin-sensitive fluorometric substrate measures the heparin level and calculates the protamine requirement at the completion of surgery; however, these assays do not indicate the degree of anticoagulation. The fluorometric assay is the less expensive of the two assay measuring heparin, but it requires an experienced technologist to perform the test.

Cardiopulmonary Bypass↗

Viscoelastic measurement of clot formation: a new test of platelet function.

Assessment of platelet function presents a challenge to the investigators in the clinical field. An instrument, Sonoclot, is described which measures changes in the viscoelastic properties (clot impedance on a vibrating probe) of plasma as it is recalcified. Platelet poor plasma (PPP) and platelet rich plasma (PRP) show distinct and characteristic Sonoclot tracings. Tracings of PPP show a lag period and a primary wave. These parameters correspond to recalcification time and fibrin polymerization. Tracings of PRP show, in addition, a secondary wave and a downward wave. These parameters correspond to the incorporation of platelets in the clot and retraction of the clot. The PRP parameters are influenced by the number and quality of the platelets. This instrument was utilized to assess the platelet function in patients after coronary artery bypass surgery (CAB). In 69 patients studied, 20 patients did not have excessive bleeding. The clot impedance tracings in this group were normal. Twenty-four patients had excessive bleeding, normal clot impedance, and coagulation tests indicating the possibility of surgical bleeding. This was confirmed in 22 (92 percent) patients upon exploration to control bleeding. Twenty-five patients had excessive bleeding, normal coagulation tests and abnormal clot impedance suggesting platelet dysfunction. In twenty-one (84 percent) of the patients, transfusion of platelet concentrate controlled the bleeding with corresponding correction of clot impedance. Sonoclot studies are quick and easy to perform, and appear to be a valuable and reliable adjunct in the diagnosis of hemostatic problems after CAB surgery.

Bleeding Time↗

Acute lymphoblastic leukemia following Hodgkin's disease.

Over 100 instances of acute leukemia have been reported in the course of Hodgkin's disease. The type of leukemia almost always is nonlymphoblastic. Only five well documented cases of acute lymphoblastic leukemia (ALL) have been found by us in the world literature. One case who developed ALL six years after intensive radiotherapy for Hodgkin's disease is herewith reported. The patient responded to treatment with Prednisone, Vincristine and intrathecal methotrexate and maintained a complete remission on 6-mercaptopurine for nine months. When last seen, the bone marrow revealed a mild increase in blasts indicative of an early relapse.

Adult↗

Enzyme labeled immunosorbant assay (ELISA) for detection of platelet antibodies.

Although it is widely accepted that patients with immune thrombocytopenia produce platelet antibodies, the demonstration of such antibodies has been difficult and time consuming. A simple and quick enzyme linked immunoassay for platelet antibodies is presented. The platelet associated IgG is coupled with alkaline phosphatase labeled anti-IgG. The resultant complex is determined spectrophotometrically using p-nitrophenyl phosphate as substrate. With this technique, excess of IgG on platelets was detected in 24 out of 33 patients (72 percent) with immune thrombocytopenic purpura and four out of four thrombocytopenic patients with systemic lupus erythematosus. The results of this assay correlate quantitatively with Dixon er al3 complement lysis inhibition assay (r = 0.82).

Autoantibodies↗

Iron metabolism and its regulation. A review.

Iron metabolism and its molecular regulation are reviewed. Ferric iron is bound to mucin in the stomach and delivered to the duodenum where it can be absorbed. Iron is transported across the apical membrane of the gut mucosa by integrin. Once within the mucosal cell, iron may be stored, utilized in protein synthesis, or exported to the serum. In the serum, iron is carried by transferrin. Diferric transferrin binds to transferrin receptor on the surface of cells and is endocytosed. In the cell, iron is bound to high and low molecular weight ligand and is thought to shuttle iron within the cell. Iron can be stored intracellularly within ferritin, or can be utilized in a number of iron containing proteins synthesized by the mitochondrion, including heme, aconitase, and cytochromes. The first chain of enzymes in the biosynthesis of heme is erythroid 5-aminolevulinate synthase (eALAS). Intracellular iron concentration regulates the synthesis of ferritin, transferrin receptor, and eALAS, thus controlling our iron metabolism. Iron regulates these proteins post-transcriptionally via iron responsive elements (IRE), which are highly conserved stem-loop structures found in messenger ribonucleic acid (mRNA), and an IRE binding protein (IRE-BP), which responds to increased intracellular iron concentrations by binding the IRE, and repressing mRNA translation or stabilizing the mRNA, depending on whether the IRE is located in the upstream or downstream untranslated regions of the mRNA. Cellular responses to iron depletion and iron over-load can be explained in terms of these regulatory mechanisms.

Animals↗

Comparison of zeta sedimentation ratio with Westergren sedimentation rate.

Zeta sedimentation ratio (ZSR) is a simple, rapid and reproducible test which is not influenced by variables like sex and anemia. There is good correlation with Westergren erythrocyte sedimentation ratio (ESR) in normal and hospital population. Limitation of packing force affects the use of the procedure in polycythemia and in patients with ZSR greater than 80%.

Anemia↗