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Biomedical subjects

A Nasir

Publications and source records attributed to A Nasir.

At least 19 recordsLinked to original sources
PubMed1999

B7-1 overexpression by thymic epithelial cells results in transient and long-lasting effects on thymocytes and peripheral T helper cells but does not result in immunodeficiency.

The B7-1 (CD80) molecule provides costimulatory function for the activation of T helper lymphocytes upon encounter with antigen. To investigate the role of this molecule in thymocyte maturation, we have generated transgenic (Tg) mice in which CD80 expression is driven by the keratin 14 promoter (K14). This overexpression of CD80 resulted in the loss of detectable cell surface CD28 expression on thymocytes and a significant reduction in both the surface T cell receptor expression and the ratio of CD4(+) to CD8(+) single-positive thymocytes in Tg animals compared to nontransgenic (non-Tg) controls. While many of these defects were transient, the significant decrease in CD4(+) versus CD8(+) T cell ratio persisted peripherally. Peripheral T cells from these Tg mice were found to be significantly hyporesponsive to T cell mitogens and in mixed leukocyte reaction, effects that our data indicate are due to reduced IL-2 production by Tg T cells upon activation. Despite these functional defects, immunization with both complex and simple protein antigens produced no differences in the proliferative or humoral responses to these antigens between Tg and non-Tg groups. These data indicate that thymic CD80 signaling results in the deletion of significant numbers of CD4(+) T cells but does not culminate in antigen-specific immunodeficiency.

Animals↗
PubMed1999

Involvement of corticosterone in food intake, food passage time and in vivo uptake of nutrients in the chicken (Gallus domesticus).

To evaluate the effect of corticosterone on nutrient transport, 10-week-old male chickens were grouped in 4 categories and treated as follows: sham-operated, adrenalectomised, corticosterone (4 mg/kg injected subcutaneously for 5 d) in both sham-operated and adrenalectomised. The food intake, food passage time and uptake of calcium, phosphorus and glucose were determined by standard procedures. Corticosterone administration to both sham-operated and adrenalectomised groups stimulated significantly higher food intake, delayed food passage time and increased uptake of calcium, phosphorus and glucose, as compared to sham-operated control and adrenalectomised groups. Corticosterone administration increased absorption of these nutrients significantly more in the adrenalectomised group than in the sham-operated controls. Corticosterone also significantly elevated the plasma concentrations of these nutrients. The responses to the hormone were significantly greater in adrenalectomised birds. It is concluded that corticosterone increases food intake and retention and the absorption of calcium, phosphorus and glucose in the alimentary tract.

Adrenalectomy↗
PubMed1998

Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1.

B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase protection assays to detect inflammatory cytokine transcripts at hapten application sites indicated that B7-1 Tg mice responded to hapten application with increased TNF-alpha, IL-6, and TNF-beta transcripts compared to NTg mice. Thus, hapten-induced ear swelling in these Tg mice may be mediated by enhanced inflammatory cytokines during the early phase (1-14 days). IFN-gamma-producing lymphocytes may be responsible for the late phase of the ear-swelling response (14-42 days). These data indicate that B7-1 overexpression by KC in mouse skin directly or indirectly affects the nature of cutaneous inflammation induced by haptens and irritants.

Animals↗
PubMed1998

CD86 (B7-2), but not CD80 (B7-1), expression in the epidermis of transgenic mice enhances the immunogenicity of primary cutaneous Candida albicans infections.

Transgenic (Tg) mice whose epidermal keratinocytes constitutively overexpress either B7-1 (CD80) or B7-2 (CD86) exhibited exaggerated cutaneous delayed type hypersensitivity (DTH) to haptens compared to non-Tg mice. To determine whether enhanced DTH in these Tg mice is seen in response to cutaneous fungal infections, a primary infection with Candida albicans was established by inoculating this organism on the occluded skin of Tg and non-Tg mice. These infections resolved 7 days after removal of occlusive dressing in all three groups of mice, without evidence of exaggerated inflammation in either the Tg or non-Tg mice. Only B7-2 Tg mice developed enhanced Th1-lymphocyte-mediated immune responses to C. albicans antigens after resolving this infection: enhanced footpad swelling in response to intradermal C. albicans antigens, enhanced production of mRNA encoding Th1 lymphokines in draining lymph nodes, and increased gamma interferon secreted into culture supernatants by lymph node T lymphocytes stimulated with Candida antigens in vitro. Lastly, Western blotting of sera from mice that had resolved this fungal infection indicated that only B7-2 Tg mice recognized a wide range of Candida-associated antigens. These data suggest that these two costimulatory molecules, when expressed by keratinocytes, do not deliver identical signals to C. albicans antigen-reactive Th1 lymphocytes. The enhanced immune response in B7-2 Tg mice to a cutaneous C. albicans infection demonstrates the importance of antigen presentation and costimulation in immune reactivity to fungi. Furthermore, B7-2 Tg mice may be useful in identification of protective Candida antigens.

Animals↗
PubMed1997

Expression of B7-1 by Pam 212 squamous cell carcinoma enhances tumor cell interactions with dendritic epidermal cells but does not affect in vivo tumor growth.

Direct antigen presentation of tumor-associated antigens by tumor cells to T lymphocytes may induce clonal anergy as a mechanism of escape from immune surveillance. B7-1 is a costimulatory molecule for the activation of both CD4+ and CD8+ T lymphocytes that prevents the induction of clonal anergy. Thus, the transfer of B7-1 genes into tumor cells can induce protective immunity and lead to tumor rejection of some tumors in model systems of in vivo tumor growth; however, there is no information on whether stable expression of B7-1 can affect the in vivo growth of squamous cell carcinoma, a common skin cancer. Here, we study how the stable cell surface expression of high levels of B7-1 by Pam 212, a murine squamous cell carcinoma, affects tumor cell-lymphocyte interactions (lymphocyte proliferation and cytotoxicity). Consistent with its costimulatory role, we demonstrate that B7-1 can efficiently induce dendritic epidermal T-cell proliferation in three different dendritic epidermal T-cell cell lines. In addition, B7-1 enhances dendritic epidermal T-cell cytolytic activity against Pam 212 cells in an in vitro 51Cr-release assay, which was blocked by CTLA-4/Ig fusion protein. In contrast to dendritic epidermal T cells, the expression of B7-1 does not alter Pam 212 interactions with either cytotoxic T-lymphocytes, natural killer, or lymphokine-activated killer cells. B7-1 expression by Pam 212 cells did not alter its ability to grow tumors in vivo, as their rate of tumor growth was the same as vector-transfected Pam 212 cells, which were B7-1 negative. Our studies indicate that B7-1 gene transfer into Pam 212 does not alter its tumorigenicity, because it does not alter tumor cell-lymphocyte interactions with cytotoxic T lymphocytes, natural killer cells, and lymphokine-activated killer cells. Further studies of B7-1 modified Pam 212 and dendritic epidermal T cells will clarify whether T-cell receptor-gamma/delta-bearing T lymphocytes can play a role in immunotherapy of Pam 212 squamous cell carcinoma.

Animals↗
PubMed1995

Human keratinocytes regulate their expression of B7/BB-1 antigen by a unique, calcium-dependent mechanism.

Previous studies of normal human keratinocytes have indicated that these cells express BB-1 antigen, an important adherence molecule usually associated with "professional" antigen-presenting cells. We studied freshly isolated epidermal cells and noted that the frequency of BB-1-positive cells in normal human skin varied from 2.6 to 7.4% of total epidermal cells. Two-color flow cytometry confirmed that keratinocytes were the major cell in the epidermis that expressed BB-1, because less than 10% of total epidermal Langerhans cells were positive for BB-1. Northern blot analysis of RNA extracted from normal human epidermis revealed low levels of 1.7-kb B7-1 transcripts, which were independent of the presence of epidermal Langerhans cells, again indicating that such transcripts were derived from keratinocytes. Keratinocytes cultured in medium containing low concentrations of extracellular calcium (0.07 mM) expressed low levels of cell-surface BB-1. However, keratinocytes cultured in medium with higher levels of extracellular calcium (1.5 mM) lost cell-surface expression of BB-1. Similarly, low-calcium keratinocytes expressed the 1.7- and 2.9-kb B7-1 transcripts, whereas high-calcium keratinocytes expressed only the 1.7-kb transcript. Studies of the cell-surface expression of BB-1 by plastic adherent monocytes indicated that such cells do not respond to similar changes in extracellular calcium concentrations. Calcium-induced differentiation of keratinocytes regulates the expression of BB-1 antigen as well as transcripts, which is a novel mechanism for the regulation of this molecule.

Adult↗
PubMed1995

Adhesion of Listeria monocytogenes to silica surfaces after sequential and competitive adsorption of bovine serum albumin and beta-lactoglobulin.

Adsorbed bovine serum albumin was resistant to exchange with beta-lactoglobulin, and when albumin was adsorbed from a mixture, its surface concentration increased with time. The passivating character of adsorbed albumin and its resistance to desorption were consistent with the level of Listeria monocytogenes adhesion evoked by albumin-containing protein films.

Adsorption↗
PubMed1994

Exaggerated and persistent cutaneous delayed-type hypersensitivity in transgenic mice whose epidermal keratinocytes constitutively express B7-1 antigen.

Since mouse keratinocytes are tolerogenic antigen presenting cells for T cell activation, the expression of second signal molecules such as B7-1 was targeted to epidermal keratinocytes (KC) in vivo in transgenic mice. The expression vector used to create transgenic mice consisted of a keratin 14 promoter fused 5' to the full length open reading frame of the cDNA encoding mouse B7-1 (between 10 and 30 copies of the transgene per genome). Expression of B7-1 cell surface protein was assessed by in situ immunostaining of cryostat sections of tail skin with CTLA-4/Ig fusion protein, revealing high levels of cell surface expression of B7 by all epidermal KC of transgenic mice, and a lack of such expression in nontransgenic animals. The skin of such transgenic mice (derived from three different founder mice) was grossly and histologically normal, with normal numbers of Langerhans cells and dendritic epidermal T cells. Immunologic challenge of transgenic mice with epicutaneous haptens such as fluorescein isothiocyanate revealed enhanced and persistent delayed-type hypersensitivity responses, with an altered kinetics of resolution when compared with nontransgenic controls. These data indicate that in normal, nontransgenic mice, tolerogenic antigen presentation by KC plays an important physiologic role in damping T cell-mediated inflammation in the skin by competing with professional APC for TCR occupancy in antigen specific T-lymphocytes that migrate into the epidermis. This also implies that altered regulation of B7-1 gene expression by epidermal cells may account for skin "hyperresponsiveness" encountered in some chronic dermatologic disorders.

Abatacept↗
PubMed1993

Cost assessment of the evaluation of heart murmurs in children.

Echocardiography available directly to primary care physicians represents an alternative strategy to pediatric cardiology consultation for childhood heart murmur evaluation. A decision analysis model compared the costs of two diagnostic strategies: (1) echocardiography first, referral to the cardiologist if appropriate; and (2) cardiologist evaluates murmur, echocardiography if appropriate. The model incorporated probability of heart disease, frequency of cardiologist-ordered echocardiography, and echocardiography results established by review of 388 records of consecutive patients evaluated for murmurs in a pediatric cardiology clinic. Echocardiography-first strategy costs were $257 greater than referral-strategy costs. Referral-strategy advantages were not highly sensitive to changes in model assumptions. Pediatric cardiology consultation is the preferred approach provided (1) consultation costs are moderate, (2) echocardiography costs are moderate to high, and (3) the rate at which the cardiologist orders echocardiography for patients with innocent murmurs is low.

Cardiology↗
PubMed1992

Centrifugal elutriation of large fragile cells: isolation of RNA from fixed embryonic blastomeres.

In order to analyze the RNA populations present in different cells of very early embryos, we have developed a protocol to purify these large blastomeres using counterflow centrifugal elutriation (CCE). This procedure employs ethanol fixation to stabilize the cells against shear forces encountered during CCE. Using this method, we fractionated the three different blastomere types of the 16-cell sea urchin embryo, the micromeres, mesomeres, and macromeres, achieving 96, 94, and 96% mean purities, respectively. We show here that intact RNA is recovered with equal efficiency from each blastomere preparation. Using this method, we have identified several RNAs that are distributed non-uniformly among these cells.

Animals↗
PubMed1992

Early mRNAs, spatially restricted along the animal-vegetal axis of sea urchin embryos, include one encoding a protein related to tolloid and BMP-1.

The cloning and characterization of cDNAs representing four genes or small gene families that are coordinately expressed in a spatially restricted pattern during the very early blastula (VEB) stage of sea urchin development are presented. The VEB genes encode multiple transcripts that are expressed transiently in embryos of Strongylocentrotus purpuratus between 16-cell stage and hatching, with peak abundance 12 to 15 hours post-fertilization (approximately 150-250 cells). The VEB transcripts share the same spatial pattern in the early blastula embryo: they are asymmetrically distributed along the animal-vegetal axis but their distribution around this axis is uniform. Thus, the VEB transcripts are the earliest messages to reveal asymmetry along the primary axis in the sea urchin embryo. The temporal and spatial patterns of VEB transcript accumulation are not consistent with involvement of these gene products in cell division or in tissue-specific functions. Furthermore, VEB messages cannot be detected in either ovary or adult tissues, suggesting that these genes function exclusively during embryogenesis. We suggest that the VEB genes function in constructing the early blastula. Two VEB genes encode metalloendoproteases: one (SpHE) is hatching enzyme and the other (SpAN) is similar to bone morphogenetic protein-1 (BMP-1; Wozney et al., Science 242: 1528-1534, 1988) and the Tolloid gene product (tld) (Shimell et al., Cell 67: 459-482, 1991). Several lines of evidence suggest that the VEB genes are regulated directly by factors or regulatory activities localized along the maternally specificed animal-vegetal axis.

Animals↗
PubMed1987

Sequences of two kinetoplast minicircle DNAs of Trypanosoma (Nannomonas) congolense.

Random minicircle DNA molecules were released from isolated kinetoplast network DNA of Trypanosoma congolense by BamHI digestion and cloned into plasmid pUC19. The sequences of two cloned minicircles (958 bp and 964 bp) were determined. Both minicircles contain the 13 bp sequence, 5'-GGGGTTGGTGTAA-3', thought to be the replication origin of minicircles in other trypanosomatids. The two minicircles have extensive homology in the 120 bp preceeding, and the 20 bp following, this 13-mer but only scattered homology elsewhere. Both possess tandem repeats downstream of the 13-mer. Comparison of these minicircles with minicircle sequences from other trypanosomatids reveals that they have the same general sequence organization as the others although only the 13-mer and its flanking regions are homologous.

Animals↗
PubMedDate not supplied

Inflammatory pseudotumor of the spleen associated with a cavernous hemangioma diagnosed at intra-operative cytology: report of a case and review of literature.

This report presents a case of a 40 year old Caucasian female with a 15 cm inflammatory pseudotumor (IPT) of the spleen with associated areas of splenic hemangioma of the cavernous type. Abdominal CT showed a largely fatty splenic mass with enhancing septations, and scattered calcifications, and a small density in the liver. Grossly, the splenic lesion showed a lobulated cut surface with areas of myxoid change, necrosis, hemorrhage and cystic softening. The diagnosis of IPT was suggested at intraoperative consultation using cytologic smears and was, subsequently confirmed on permanent sections. Histologically, the lesion consisted of a densely collagenized spindle cell stroma with patchy aggregates of lymphocytes and plasma cells, and scattered foci showing hemosiderin-laden macrophages extracellular calcium deposits and osseous metaplasia. The stromal spindle cells were immuoreactive for smooth muscle actin and vimentin confirming their myofibroblastic phenotype. There were extensive areas of infarction within the mass. The patient, however, remained asymptomatic preoperatively. Histologic analysis in this case raises the possibility that low grade, perhaps repetitive, trauma to the hemangioma may have resulted in intralesional hemorrhages which, through a process of organization, may have evolved into this sizable inflammatory pseudotumor. In addition, this report reviews the current literature on the clinical significance and presentation, morphologic and immunohistochemical findings, prognosis, differential diagnosis, pathogenesis and therapy of the splenic IPT.

Adult↗
PubMedDate not supplied

Loss of heterozygosity in papillary and follicular thyroid carcinoma: a mini review.

Inactivation of tumor suppressor genes is an important mechanism in the development of most cancers. This can be detected by determining loss of heterozygosity (LOH) on highly polymorphic loci on chromosomes. Many investigations to determine LOH in papillary and follicular thyroid carcinoma have been performed using bulk tissue which was fresh, snap frozen, or has been formalin-fixed/paraffin-embedded. Loss of heterozygosity is more frequently encountered in follicular than papillary carcinoma. Laser Capture Microdissection (LCM) may be useful to ascertain if there is a pattern of LOH for various histologic forms and variants of thyroid carcinoma.

Carcinoma, Papillary, Follicular↗
PubMedDate not supplied

Neoplasms during the progression of pregnancy.

Restricting this review to dealing with pregnancy and its interaction with neoplasms limits us to the child-bearing years. Neoplasms may appear at all stages of species with true tissues and the incidence of malignancy in pregnancy is estimated to be 1:1,000. Almost 50% of these tumors are cervical cancers, followed by breast cancer, with an incidence of approximately 0.03%. The pregnant woman, in the same person, exhibits controlled growth (the pregnancy) and uncontrolled growth (the malignancy). In younger women, the neoplasms represent early stages of biological development and seem to arise practically from all maternal tissues. Geriatric changes in the neoplastic growth processes are missing. This article encompasses a review of the integration of neoplasms, the maternal body, the fetus and the placenta. The morphological and biochemical integration of the different processes is diversified. Mainly, we would like to address the interaction between pregnancy and common human malignancies like breast, cervix, and melanoma, but we will also review rare neoplastic complications. This way it is possible to treat the combined growth processes as they evolve from the initiated sperm, the ovum and continue via the placental development. These processes lead to the fetus and, in the pathological sense, to childhood complications, though most cases develop only portions of the process.

Breast Neoplasms↗
PubMedDate not supplied

Apoptosis and pathogenesis of viral hepatitis C--an update.

Hepatitis C virus is a major causative agent of chronic liver disease. Viral genotype, mutations, virus-host interaction, expression of viral proteins and host immune-reaction are important factors in the pathogenesis of HCV infection. Precise pathogenesis and perpetuation of hepatocellular injury in hepatitis C viral infection remain unclear. Proposed mechanisms include direct viropathic effect, the host immune response mediated through cytotoxic T lymphocytes, both viropathic and cytopathic effects, and macrophages/monocytes. Apoptosis occurs both in acute or chronic hepatitis and has been suggested to be mediated through Fas antigen. In HCV infection, Fas expression is up-regulated in the liver cells in line with the severity of liver inflammation. When HCV-specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that transduces the apoptotic death signal to Fas-bearing hepatocytes resulting in their destruction. Thus, the Fas system plays an important role in liver cell injury by HCV infection. Possible inducers of apoptosis in hepatitis C include cytokines, especially tumor necrosis factor-alpha (TNF-alpha), released by inflammatory cells, and acting through TNF and other cytokine receptors.

Apoptosis↗