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Biomedical subjects

S Rajaraman

Publications and source records attributed to S Rajaraman.

At least 127 records · Page 7Linked to original sources

Acute monoblastic leukemia with a single chromosomal rearrangement involving breakpoints on chromosomes 8 and 16, 46, XX, t(8;16)(p11;p13).

We report a case of acute nonlymphoblastic leukemia (M5) with a rare cytogenetic abnormality involving chromosomes 8 and 16, t(8;16)(p11;p13). The leukemic blasts were determined to be monocytic by cytochemical and immunochemical studies. Morphological changes of the leukemic cells in response to phorbol myristate acetate further supported their identification as monocytic in nature. This chromosomal abnormality has apparently been reported only thrice in the literature. Translocation (8;16)(p11;p13), though rare, may be of primary importance in the process of leukemogenesis in some cases of histiocytic/monocytic malignancies.

Acute Disease↗

Auer rod-like inclusions in prolymphocytic leukemia.

Auer rod-like inclusions (ARLI) can be seen in B cell malignancies but are very rare in prolymphocytic leukemia (PLL). Prolymphocytes with ARLI from a patient with PLL were examined using cytochemical and immunochemical techniques and transmission electronmicroscopy (EM). The lymphoblastic cells gave a positive reaction with antibodies to the gamma heavy chains and kappa light chain. On EM the ARLI were 1-2 micron long, consisting of election-dense crystalline matrix, with a periodicity of 60 A and contained within a single unit membrane. The production of IgG by PLL cells with ARLI has not been previously reported. It is emphasized that in PLL the lymphoblasts can have inclusions resembling Auer rods. Cytochemical and immunochemical studies should be done to avoid a misdiagnosis of acute nonlymphoblastic leukemia.

Aged↗

Aberrant expression of a chemokinetic glycoprotein in psoriatic skin.

Clinically involved and uninvolved skin samples of 6 psoriatic patients, 4 samples each of normal skin specimens, basal cell carcinoma and keratoacanthoma were studied by an indirect immunofluorescence technique. The monospecific antibody used in this study was directed against a 30 kD glycoprotein, normally expressed by the terminally differentiated corneocytes. Functional characterization of this glycoprotein was evaluated by neutrophil cell movement assays. The involved and uninvolved skin of psoriatic patients expressed the 30 kD glycoprotein not only in the stratum corneum but in all the viable epidermal layers as well. Functional studies revealed this glycoprotein to be a potent chemokinetic molecule. These results suggest that the 30 kD glycoprotein is an intrinsic chemokinetic molecule of the terminally differentiated corneocytes, and its precocious and aberrant expression in psoriatic epidermis is potentially responsible for some of the pathophysiologic aspects of psoriasis.

Chemotactic Factors↗

Establishment and characterization of a human myeloid cell line from Philadelphia chromosome-negative myeloblastic leukemia arising in a patient with myelodysplastic syndrome.

A new hematopoietic cell line derived from a patient with Philadelphia chromosome (Ph1)-negative myeloblastic leukemia arising from a form of myelodysplastic syndrome (MDS) is described. This cell line, designated TMM, consists of immature cells with the morphological characteristics of young myeloblasts and grows in suspension culture with a doubling time of about 30 hours. By cytochemical analysis the cultured cells were positive for acid phosphatase. They were free of the Epstein-Barr virus-associated nuclear antigen as well as terminal deoxynucleotidyl transferase. Further phenotypic analysis revealed the expression of the myelomonocytic-specific antigen Leu-M1 and receptors for the Fc portion of IgG. Partial differentiation of these cells could be induced by dimethyl sulfoxide, tetradecanoyl phorbol acetate, or hypoxanthine and resulted in cells of the myeloid series expressing lysozyme and receptors for the C3b complement protein. The karyotype was 46,XY, lacked the Ph1 chromosome, and displayed no abnormalities at the light microscopic level. No rearrangement of the bcr-c-abl gene complex was found. This cell line should be useful for studying an important type of the heterogeneous population constituting Ph1-negative myeloblastic leukemia, arising in this instance from MDS, as well as for studying differentiation and proliferation of human pluripotent stem cells.

Antigens, Neoplasm↗

Calcitonin gene-related peptide: possible tumor marker for medullary thyroid cancer.

We have sought to determine whether medullary thyroid carcinoma (MTC) released calcitonin gene-related peptide (CGRP) in vivo. MTC cells were inoculated from tissue culture into eight Wag-Rij rats. One month later blood was drawn before and after the intravenous injection of calcium, and plasma levels of CGRP and calcitonin (CT) levels in that blood were determined by radioimmunoassay. The tumor was examined for content of CGRP and of CT by means of radioimmunoassay and immunocytochemistry. The tumor was divided and portions were passed to another eight rats. One month later, the studies were repeated. The tumor was passed two additional times (four passages in all). Controls consisted of non-tumor-bearing Wag-Rij rats. Basal levels of plasma CGRP in control rats (7 +/- 1 ng/ml) were unaffected by calcium stimulation. In tumor-bearing rats, the plasma CGRP level, which was initially slightly elevated (15 +/- 7 ng/ml), rose progressively with passages to 279 +/- 79 ng/ml in the third passage and fell to normal values at the end of passage four. Hypercalcemia had no effect on plasma CGRP levels in tumor-bearing rats but did stimulate the release of CT in both control and tumor-bearing rats, although it is not clear whether this release was from the tumor or from normal thyroid parafollicular cells in these tumor-bearing rats. We conclude that rat MTC synthesizes and releases CGRP but, unlike CT, CGRP appears unresponsive to calcium stimulation.

Animals↗

Effect of oxygen on the clonal growth of adherent cells (CFU-F) from different compartments of mouse bone marrow.

We have used collagenase to isolate cell populations from different compartments of mouse bone marrow. Cells were obtained from the shaft of the femur, the endosteum, and compact bone. We have studied the growth-enhancing effects of physiologically low oxygen levels on fibroblast colony-forming unit (CFU-F) growth in vitro. Low oxygen levels (0.1%-10% O2) increased CFU-F formation 1.8- to 2.8-fold. However, cells from the compact bone consistently grew with much higher efficiencies (12- to 31-fold) than did cells from femoral cavity and endosteal areas. These data indicate the usefulness of enzymatic methods of isolating cells from compartments of bone and the use of low oxygen atmosphere to enhance stromal cell growth in vitro.

Aerobiosis↗

Isolation and characterization of a 30 kDa membrane glycoprotein from human stratum corneum.

Using iodinated concanavalin A in conjunction with gel electrophoresis, we have identified a 30 kDa glycoprotein in the stratum corneum of human skin. We isolated this glycoprotein by extraction in nonionic detergent, affinity chromatography and preparative gel electrophoresis. It binds to concanavalin A but not to three other lectins. The purified glycoprotein migrates at 30 kDa whether or not reducing agents are present. It is rich in histidine and lysine, but lacks arginine, proline, tyrosine and methionine. It is clearly distinct from filaggrin. We prepared a monospecific polyclonal antibody to this glycoprotein and localized it by immunohistochemistry exclusively to the cell membrane of corneocytes. We postulate that the glycoprotein may play a role in the cohesion and desquamation of corneocytes.

Adult↗

IgA-associated glomerulonephritides: a study with monoclonal antibodies.

Thirty-six renal biopsies from patients with various glomerulonephritides which exhibited prominent IgA deposits were studied by indirect immunofluorescence technique utilizing monoclonal antibodies specific for alpha chain (IgA), IgA1 and IgA2 subclasses, secretory IgA, and secretory component. The ability of the IgA deposits to bind free secretory component in vitro was examined in five biopsies of IgA nephropathy of Berger and in five biopsies of lupus nephritis. All the biopsies revealed IgA1 deposits. Associated IgA2 was found in lupus nephritides and hepatic glomerulopathy. Secretory IgA and free secretory component were not detected in any biopsy. In situ free secretory component binding was demonstrated in IgA nephropathy of Berger but not in lupus nephritides. These results indicate that polymeric IgA1 molecules are the chief nephritogenic antibodies in IgA nephropathy of Berger, that there is a high frequency of association of IgA1 and IgA2 in lupus nephritides and, perhaps, hepatic glomerulopathy, and that secretory IgA does not appear to play a role in IgA-associated glomerulonephritis.

Antibodies, Monoclonal↗

Role of marrow stromal cells in the establishment of a transformed lymphoblastic B-cell line from a normal human subject.

A monoclonal human B-lymphoblastoid cell line (UTMB-460) arose spontaneously from the bone marrow of a normal healthy woman who was seropositive for an EB-virus infection. Chromosomally, the UTMB-460 cells are near tetraploid, with a specific translocation (8;9) (p11.2; p24), and have surface IgMk. The UTMB-460 cells are resistant to killing in vitro by spontaneous and rIFN alpha 2 and rIL-2 stimulated NK cells from the patient and other normal subjects, but are killed by lymphokine activated killer cells. The index patient has not developed leukemia/lymphoma during the follow-up interval of 22 months. The growth of UTMB-460 cells is supported by undefined growth factors in FCS and by BCGF in the absence of FCS. rIL-2 stimulates DNA synthesis by UTMB-460 cells. The UTMB-460 cells were adherent to the normal MSC in the primary culture and show specific heterotypic adherence to normal MSC when compared to skin fibroblasts. In addition, 6/6 normal marrow stromal cells and 4/6 normal skin fibroblasts induced growth of colonies from UTMB-460 cells. These data suggest that MSC interacted with the transformed cells (UTMB-460) in vitro and played a critical role in the establishment of the UTMB-460 cell line.

Adult↗

Endogenous lectin from terminally differentiated epidermal cells.

We isolated a concanavalin A (Con-A)-binding glycoprotein from human stratum corneum by nonionic detergent extraction, lectin affinity chromatography, and preparative gel electrophoresis. This glycoprotein migrates as a single band at 40 kilodaltons at sodium-dodecyl-sulfate gel electrophoresis with or without the presence of 2-mercaptoethanol. It was shown to have a heterogeneous distribution between pH 5.6 and 7.6 by isoelectric focusing. The glycoprotein is histidine rich (10.4%) but is distinct from other histidine-rich proteins (epidermal filaggrin and the histidine-rich glycoprotein from serum). It does not bind to lectins specific for L-fucose or alpha-D-galactose. We prepared a monospecific polyclonal antibody to the 40-kilodalton glycoprotein; at the ultrastructural level, it cytoimmunolocalizes exclusively to the membranes of the stratum corneum. A unique feature of the glycoprotein is that it is an endogenous lectin: it hemagglutinates trypsinized and gluteraldehyde-fixed rabbit erythrocytes. The inhibition of its hemagglutination was found to be greatest with amino sugars, down to a saccharide concentration of 10(-5) mM. Such a high affinity of binding at the cell surface suggests that this glycoprotein is a major carbohydrate-binding, cross-linking molecule that holds adjacent corneocytes together in the stratum corneum. We hypothesize that this lectin plays a role in the adhesion and desquamation of the stratum corneum.

Amino Acids↗

Suppressor-cytotoxic T-lymphocyte panniculitis.

A 3 1/2-year-old girl had fever and nonsuppurative panniculitis. Biopsies revealed lobular lymphocytic panniculitis. An extensive evaluation of the patient for infectious and other systemic diseases yielded negative results. Although the number of peripheral T lymphocytes was normal, suppressor-cytotoxic (OKT8) lymphocytes predominated in the subcutis of the lesions. Suppressor-cytotoxic T-lymphocyte panniculitis may represent a unique type of panniculitis.

Adipose Tissue↗

Modified distribution of epidermal glycoproteins in the nude mouse.

The nude mouse is an athymic mutant whose immunological deficiency has been exploited for transplantation of normal and diseased xenogeneic tissue. Histologically, its skin has no unusual features apart from the absence of hair. We report here a biochemical study of its epidermis, with comparison to the hairless mouse (which is devoid of hair but otherwise functionally normal). The epidermal glycoproteins were probed with the lectin, concanavalin A (Con A). Fluorescein isothiocyanate (FITC)-Con A overlays of cryostat skin sections gave a similar fluorescent pattern for both mouse strains: all the viable epidermal cell layers were labeled but not the stratum corneum. In contrast, when different populations of keratinocytes that were separated on Percoll gradients were analyzed by gel electrophoresis, and the gels then overlaid with iodinated Con A, all the epidermal layers, including the stratum corneum, were labeled. For all the epidermal cell layers there are substantial differences between the two mouse strains. We observe changes in the glycoprotein distribution with the stage of differentiation. Comparison with our earlier data for human epidermis indicates that the discrepancies between the nude mouse and the hairless mouse are much greater than those between the latter and man. The most striking difference is the absence in the stratum corneum of the nude mouse of a 40 K glycoprotein which is the dominant feature for the hairless mouse and for man. The gel patterns point to functional discrepancies in the epidermis of the nude mouse, particularly in the stratum corneum, not evident histologically or with FITC-Con A.

Animals↗

Carcinoma in situ of the vulva. A clinicopathologic study of 50 cases.

The authors reviewed 50 cases of carcinoma in situ of the vulva treated at the University of Texas Medical Branch, Galveston, from 1975 to 1984. Sixty-two percent of the patients were premenopausal. The most frequent complaint was vulvar itching. Twenty-six percent of the patients were asymptomatic. Recurrences were frequent (25%) and were associated with multifocal lesions, involved surgical margins and the bowenoid histologic type. Superficially invasive carcinoma was detected in 8% of patients, mostly postmenopausal women with simplex histologic types. Immunohistochemical studies failed to detect papillomavirus- or herpesvirus-associated antigens in any of the cases. Follow-up of 48 patients from six months to ten years revealed no mortality from invasive cancer.

Adult↗

Normal human marrow stromal cells induce clonal growth of human malignant T-lymphoblasts.

The effect of marrow stromal cells (MSC) on the clonal growth of a human malignant T-lymphoblast (MTL) cell line was investigated in a bilayer culture system. The MSC consistently stimulated clonal growth of MTL, and no stimulatory humoral factor was present in the medium conditioned by the MSC. These observations and other reports suggest that marrow stromal cells may provide a microenvironment in vivo that is not only conducive to the growth of malignant lymphoblasts, but may actually enhance proliferation of malignant T-lymphoblasts in the bone marrow.

Alkaline Phosphatase↗

Localized vulvar pemphigoid in a child.

Bullous pemphigoid often affects the elderly but is not common in children. At least two localized variants, cicatricial pemphigoid and localized, chronic pemphigoid of Brunsting-Perry, have been described. A case of bullous pemphigoid in a 9-year-old girl was unusual because erosions were limited to the vulvar area. Other bullous dermatoses were considered in the differential diagnosis. Histopathologic examination and immunofluorescence microscopic studies, as well as immunoelectron microscopic studies, which yielded unique results, were performed to confirm the diagnosis.

Child↗

Glomerulonephritis with coexistent immune deposits and antibasement membrane activity.

Six patients with coexistent antiglomerular basement membrane disease and granular immunoreactants in the glomerular basement membrane and mesangium are discussed. These six patients represent 35% of all patients with antiglomerular basement membrane nephritis examined over 10 years. All patients presented with acute, oliguric renal failure, and rapid deterioration in renal function. In all patients the pathogenetic role of the antiglomerular basement membrane antibody was confirmed by the demonstration of linear deposits of IgG along the glomerular basement membrane and antiglomerular basement membrane antibody activity in the serum or renal eluates, or both. Evidence for the existence of concurrent immune aggregates was obtained by immunofluorescence studies and electron microscopy. Radioimmunoassays, which were performed in two patients to detect circulating immune complexes, however, yielded negative results. The possible mechanisms concerned in the evolution of this condition and their potential implications are reviewed.

Adult↗

Immune complex disease complicating diabetic glomerulosclerosis.

We report immunopathologic findings observed in renal biopsies of 18 patients with diabetic glomerulosclerosis and associated glomerulonephritis. 10 patients had nodular and 8 patients diffuse diabetic glomerulosclerosis. Focal proliferative glomerulonephritis (4 patients), membranous glomerulonephritis (3 patients), postinfectious glomerulonephritis, Henoch-Schönlein nephritis, IgA nephropathy of Berger (1 patient each), and mesangiopathic glomerulonephritis (8 patients) were the superimposed conditions. In patients with diabetic renal disease, a rapid loss of renal function or an atypical urinalysis could be the expression of a superimposed immune complex disease. Because of functional and biochemical alterations, the glomeruli of diabetic patients may be more susceptible to immune-mediated injury.

Adult↗

A lymphocytotoxic factor(s) in plasma of patients with minimal change nephrotic syndrome: partial characterization.

The incidence, relationship to clinical disease, and physical characteristics of a plasma cytotoxic factor(s) were studied in steroid-responsive minimal change nephrotic syndrome (MCNS) and other renal diseases. Plasma activity was found in 76% of 67 children with MCNS and in 67% of 9 children with focal segmental sclerosis (FSS). Of 31 normal adults and children and 7 adults with membranous glomerulonephritis, only 1 individual had toxic plasma. In MCNS, degree of plasma activity was not related to clinical disease, prednisone dosage, or serum levels of IgG or alpha-2-macroglobulin. The active factor(s) was found more frequently in plasma than in serum, was heat stable and nondialyzable by selected filtration, and was approximately 100,000 to 300,000 molecular weight. By DEAE column chromatography, activity coincided with fractions containing IgA and IgM but not IgG. While the nature of the plasma factor(s) has not been identified, these data indicate that MCNS plasma may adversely affect lymphocyte viability by a slow process of cytotoxicity requiring 24 or more hr, and that such plasma activity occurs frequently in children with MCNS and also with the more severe FSS.

Adolescent↗