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S Amini

Publications and source records attributed to S Amini.

At least 55 records · Page 3Linked to original sources
PubMed1995

A 39-kD DNA-binding protein from mouse brain stimulates transcription of myelin basic protein gene in oligodendrocytic cells.

The MB1 regulatory sequence of the myelin basic protein (MBP) gene spanning between nucleotides -14 to -50 with respect to the transcription start site is critical for cell type-specific transcription of the MBP gene, which encodes the major protein component of myelin sheath in cells derived from the central nervous system (CNS). This regulatory sequence has the ability to interact with a developmentally controlled DNA-binding protein from mouse brain that stimulates transcription of MBP promoter in an in vitro system (Haas, S., J. Gordon, and K. Khalili. 1993. Mol. Cell. Biol. 13:3103-3112). Here, we report the purification of a 39-kD protein from mouse brain tissue at the peak of myelination and MBP production that binds to the MB1 regulatory motif. Following partial amino acid sequence analysis, we have identified a complementary DNA encoding a 39-kD DNA-binding protein called pur alpha. Expression of pur alpha cDNA in the prokaryotic and eukaryotic cells resulted in the synthesis of a protein with characteristics similar to the purified brain-derived 39-kD protein in band shift competition assays. Cotransfection of the recombinant pur alpha expressor plasmid with MBP promoter construct indicated that Pur alpha stimulates transcription of the MBP promoter in oligodendrocytic cells, and that the nucleotide sequence required for binding of the 39-kD Pur alpha to DNA within the MB1 region is crucial for this activity. Moreover, transient expression of Pur alpha caused elevation in the level of endogenous MBP RNA in oligodendrocytic cells. Thus, Pur alpha, a sequence-specific DNA-binding protein upon binding to MB1 regulatory region may play a significant role in determining the cell type-specific expression of MBP in brain.

Animals↗
PubMed1995

Stimulation of alpha 1 (I) procollagen gene expression in NIH-3T3 cells by the human T cell leukemia virus type 1 (HTLV-1) Tax gene.

The mechanisms that regulate the expression of genes encoding extracellular matrix proteins in fibroblasts and other mesenchymal cells have remained elusive. Studies from several laboratories have indicated that Tax, a trans-regulatory protein from the human T cell leukemia virus type I not only augments viral gene expression but also triggers the expression of various cellular genes. Here, we examined the hypothesis that the expression of collagen genes may also be modulated by Tax. NIH-3T3 cells were simultaneously transfected with a Tax expressor plasmid and a chimeric construct containing regulatory sequences (-804 to +42 bp) of the alpha 1(I) procollagen gene (COL1A1) promoter. The results indicated that the promoter activity of the -804 to bp COL1A1 fragment increased up to 12-fold in cells expressing Tax. Deletion analysis revealed that the region of COL1A1 encompassing nucleotides -174 to -84 contained the Tax-responsive elements. A gene segment encompassing nucleotides -187 to -67, which contained this region, proved sufficient to confer Tax inducibility (2.5-fold) to a herpes simplex virus thymidine kinase promoter. Stably transfected NIH-3T3 cell clones that constitutively produce Tax displayed elevated levels of alpha 1(I) procollagen and fibronectin transcripts and increased production and accelerated processing of type I procollagen. These findings suggest that retroviral proteins may be involved in the pathogenesis of idiopathic diseases accompanied by collagen overproduction.

3T3 Cells↗
PubMed1994

Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat.

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes. Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B. The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-kappa B from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity. The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed.

Astrocytes↗
PubMed1994

Ultrastructural localization of calcium in neuromuscular junctions of smooth and skeletal muscles after aminoglycoside antibiotics treatment.

Aminoglycoside antibiotics are all capable of producing clinically significant neuromuscular paralysis. Since part of the mechanism of action of these antibiotics at neuromuscular junction is a calcium-dependent inhibition of acetylcholine release, so this experiment was carried out in vitro on both somatic (isolated rat phrenic-nerve hemidiaphragm) and autonomic neuro-effector transmission (guinea-pig ileum) using gentamicin and amikacin, to determine the calcium contents at this level. Electron microscopic observations on gentamycin- and/or amikacin-treated materials, using potassium pyroantimonate method suggest a reduction of internal calcium in nerve terminals of both preparations.

Amikacin↗
PubMed1993

Intramedullary sodium cyanide injection on respiratory and vasomotor responses in cats.

To examine the effect of hypoxia confined to the ventrolateral medulla we microinjected NaCN into the cat medulla (1.0 mm below the ventral surface) unilaterally and investigated cardio-respiratory changes. We studied anesthetized artificially ventilated animals and measured the electrical activity of phrenic and cervical sympathetic nerves and blood pressure. Histotoxic hypoxia depressed phrenic amplitude and elevated sympathetic tone and blood pressure. These responses were obtained predominantly from the region 5.0-8.0 mm caudal to the foramen caecum and 3.0-5.0 mm lateral to the midline (intermediate area). A study with 14C-cyanide showed that total and covalently bound cyanide was confined within a 1 mm diffusion sphere following microinjection. Isolated areas in both rostral and caudal medulla responded to cyanide with elevated sympathetic tone in the absence of phrenic nerve depression, suggesting dissociation of respiratory and vasomotor responses to hypoxia. Thus, the respiratory depression and vasomotor excitation produced by central hypoxia can be reproduced by hypoxia limited to discrete regions of the ventrolateral medulla.

Animals↗
PubMed1993

Evidence for stimulation of the transforming growth factor beta 1 promoter by HIV-1 Tat in cells derived from CNS.

Infection by human immunodeficiency virus type 1 (HIV-1), the etiologic agent of the acquired immunodeficiency syndrome (AIDS), is often complicated with a high incidence of neurologic disorders. It is believed that HIV-1, in addition to infecting both macroglial and microglial cells, may influence the expression of several strategic genes of uninfected neighboring or latently infected brain cells. It is suspected that the viral-encoded transregulatory protein, Tat, facilitates cross-communications between these cells. In support of this concept, earlier studies demonstrated that Tat is released from the infected cells, and has the capacity to be taken up by the uninfected cells and exert its biological activity on the responsive gene. Recent studies in several laboratories suggest the involvement of Tat in altering the expression of a limited number of cellular regulatory factors which, in turn, may mediate the altered physiology of the cells. In this communication, we demonstrate the ability of the HIV-1 Tat protein to increase expression of transforming growth factor beta 1 (TGF-beta 1), a cytokine with potent immunosuppressive activity, in human astrocytic glial cells. Implications of the Tat-mediated induction of TGF-beta 1 expression and cytokine involvement in the regulation of immune response and central nervous system (CNS) pathology are discussed.

Astrocytes↗
PubMed1993

Seroepidemiology of hepatitis B, delta and human immunodeficiency virus infections in Hamadan province, Iran: a population based study.

The epidemiologic features of HBV, HDV and HIV in the general population of Hamadan province of Iran were studied. A total of 4930 subjects (1649 males and 3281 females) constituted the study population. Seropositivity for any HBV marker was found in 25.72% of the subjects. Of these, 2.49% were carriers of HBsAg, 18.09% were positive for anti-HBs and 5.13% for anti-HBc alone. HBeAg, anti-HBC IgM, and anti-HDV were present in 13.8, 6.5 and 2.4% of HBSAg carriers, respectively. Antibody to HIV was detected in none of the 4930 sera tested. Prevalence of HBV infection was lowest in children and young adults < 19 years and highest in adults > 60 years. No significant difference was observed between the rates in males and females. Family size and prevalence of HBV infection were unrelated but an inverse relation was found between HBV infection and education. Unmarried men and women showed the lowest (18.26%) and widows and divorcees the highest (51.59%) rate of HBV infection. Our results suggest that horizontal transmission is likely to be the primary mode of acquisition of HBV infection in children and young adults. Also infection is partly transmitted before or soon after birth to babies of HBsAg-carrier mothers. Socioeconomic and demographic variables have a greater impact on the prevalence of HBV infection than blood or medical care variables in our population.

Adolescent↗
PubMed1993

Inhibition of gentamicin-induced nephrotoxicity by lithium in rat.

Daily intraperitoneal injection of gentamicin in doses of 2, 4 and 10 mg/kg/day for 5 consecutive days produced proximal tubular necrosis in male albino rats as assessed by ultrastructural findings from electron microscopic observations. With respect to nephrotoxicity, aminoglycoside antibiotics (AGs) have been shown to concentrate in the lysosomes of kidney proximal tubular cells to inhibit the activities of phospholipases A and C, including a phospholipidosis, characterized by the formation of myeloid bodies. It has been suggested that the nephrotoxicity of AGs is related to the extent of this phospholipidosis. The concurrent therapy of lithium in doses of 5 and 10 mEq/kg/day, administered subcutaneously, 24 hours prior to gentamicin administration for the same period, proved effective in reducing the gentamicin-induced phospholipidosis in kidney as judged by reduction in lysosomal myeloid bodies to an amount of 26-45 percent. It is well known that lithium interferes with phosphatidylinositol turnover and reduces the cellular availability of myoinositol which is needed for the resynthesis of membrane polyphosphoinositides. Thus, the inhibitory effect of lithium on gentamicin-induced nephrotoxicity may be due to interference of lithium with phosphoinositide cycle.

Animals↗
PubMed1992

Activation of expression of genes coding for extracellular matrix proteins in Tat-producing glioblastoma cells.

The Tat protein of human immunodeficiency virus type 1 has been increasingly implicated in directly contributing to the disease AIDS by altering the expression of strategic cellular genes. In this study we demonstrate that the presence of the human immunodeficiency virus type 1 regulatory protein Tat is associated with a significant induction in the expression of certain protein components of the extracellular matrix in glial-derived cells. Northern blot analysis reveals that in cells expressing Tat there is a marked elevation in the steady-state RNA levels for fibronectin and types I and III collagen. Metabolic labeling of the Tat-producing cells demonstrates that this induction is also reflected at the level of protein synthesis. Transient transfection experiments indicate that the presence of Tat results in increased transcription of fibronectin and alpha I type I collagen promoters. Possible mechanisms for this phenomenon and their significance with regard to AIDS are discussed.

Collagen↗
PubMed1992

TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation.

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Correction of sulfatide metabolism after transfer of prosaposin cDNA to cultured cells from a patient with SAP-1 deficiency.

The lysosomal removal of the sulfate moiety from sulfatide requires the action of two proteins, arylsulfatase A and sphingolipid activator protein-1 (SAP-1). Recently, patients have been identified who have a variant form of metachromatic leukodystrophy which is characterized by mutations in the gene coding for SAP-1, which is also called "prosaposin." All of the mutations characterized in these patients result in (a) deficient mature SAP-1, as determined by immunoblotting after SDS-PAGE of tissue and cell extracts, and (b) decreased ability of cultured skin fibroblasts to metabolize endocytosed [14C]-sulfatide. We now report the insertion of the full-length prosaposin cDNA into the Moloney murine leukemia virus-derived retroviral vector, pLJ, and the infection of cultured skin fibroblasts from a newly diagnosed and molecularly characterized patient with SAP-1 deficiency. The cultured cells infected with the prosaposin cDNA construct now show both production of normal levels of mature SAP-1 and completely normal metabolism of endocytosed [14C]-sulfatide. These studies demonstrate that the virally transferred prosaposin cDNA is processed normally and is localized within lysosomes, where it is needed for interaction between sulfatide and arylsulfatase A. In addition, normal as well as mutant sequences can now be found by allele-specific oligonucleotide hybridization of PCR-amplified genomic DNA by using exonic sequences as primers.

Antisense Elements (Genetics)↗
PubMed1992

Occurrence of colonization factor antigens I & II in enterotoxigenic Escherichia coli associated diarrhoea in Iran & correlation with severity of disease.

The occurrence of colonization factor antigens I and II (CFA/I and II) and type 1 somatic pili was investigated in 197 enterotoxigenic Esch. coli (ETEC) isolated from 197 patients of diarrhoea (aged under 3 yr) during February 1985 to March 1986 in Tehran, Iran. Among ETEC strains, 154 strains were heat-stable enterotoxin (ST) producers, 27 strains were heat-labile enterotoxin (LT) producers, and 16 strains produced both toxins. Sixty five (33%) strains showed mannose-resistant haemagglutination (MRHA) of human and/or bovine erythrocytes; of these, 51 (86%) strains were positive for CFA/I and II. Seventy one (36%) strains also exhibited type 1 somatic pili. CFA/I was found in 4 (15%) LT producing, 24 (16%) ST producing, and 2 (13%) LT/ST producing strains. In contrast, CFA/II was only found in ST producing strains (17 strains) and those producing both toxins (4 strains). Patients having CFAs-positive ETEC strains had a significantly (P less than 0.001) higher number of stool evacuation per day and a longer duration of diarrhoea than those having CFAs-negative strains. Fifty nine patients had mixed infections of ETEC strains and other enteropathogens. CFA/I or II (CFAs)-positive and CFAs-negative ETEC strains were found in 17 and 42 patients with mixed infections respectively. The mean number of stool evacuations per day was much higher in patients with ETEC and rotavirus than those with only ETEC infection (P less than 0.001). However, severity of the disease was not affected by the presence or absence of CFA/I or II in ETEC strains found in these patients.

Agglutination Tests↗
PubMed1991

The pericardial valve in the aortic position ten years later.

To assess the behavior of the pericardial valve at 10 years after implantation, the cases of 240 patients who had undergone aortic valve replacement with the standard Ionescu-Shiley (Shiley, Inc., Irvine, Calif.) bovine pericardial valve between February 1977 and December 1983 were reassessed. Follow-up of the 224 hospital survivors was 99.6% complete. Fifty-seven valve-related events occurred. Fourteen were thrombotic events (1.2%/patient-year), 28 were intrinsic tissue failures (2.4%/patient-year), 13 were cases of prosthetic valve endocarditis (1.1%/patient-year), and 2 were paravalvular leaks (0.17%/patient-year). The linearized rate for death, reoperation, or both resulting from valve-related events was 3.6%/patient-year. Time-related hazard function for the instantaneous risk of death and/or reoperation resulting from valve-related events demonstrated an exponential increase after 80 months. These data, in conjunction with our previous reports on the histologic changes in pericardial collagen and the incidence of calcification (26/28), should be considered regarding new and future generations of pericardial bioprostheses. Although this device provides good hemodynamics and carries a low incidence of thromboembolism, it has a limited durability. New generations of pericardial valves may have improved structural features, but the behavior of glutaraldehyde-fixed, formaldehyde-stored bovine pericardium as currently selected and prepared is unlikely to change.

Adolescent↗
PubMed1990

Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study we have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. We find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCVL, in glial cells. In a reciprocal experiment, the JCV early protein, the large tumor antigen, stimulates expression from JCVL and HIV-1 long terminal repeat promoter in both glial and non-glial cells. This trans-activation occurs at the level of RNA synthesis, as measured by the rate of transcription, stability of the message, and translation. We conclude that the presence of the HIV-1-encoded tat protein may positively affect the JCV lytic cycle in glial cells by stimulating JCV gene expression. Our results suggest a mechanism for the relatively high incidence of PML in AIDS patients than in other immunosuppressive disorders. Furthermore, our findings indicate that the HIV-1 regulatory protein tat may stimulate other viral and perhaps cellular promoters, in addition to its own.

Cell Line↗
PubMed1990

Regulation of the human neurotropic virus promoter by JCV-T antigen and HIV-1 tat protein.

We compared the ability of HIV-1 tat protein and JCV T-antigen in inducing transcription from the JCV late promoter, JCVL. A JCVL promoter-chloramphenicol acetyltransferase plasmid (pJCL-CAT) was transfected into human glial cells alone or together with plasmids producing T-antigen and tat protein. CAT enzyme activity obtained from the transfected cells indicated that both JCV T-antigen and HIV-1 tat proteins stimulated JCV late gene expression. However, the level of induction mediated by tat protein was significantly higher than that obtained with T-antigen. Moreover, in contrast to JCV T-antigen, tat stimulated JCVL-promoter activity over a narrow range of ptat expressor plasmid concentration. Co-transfection of both T-antigen and tat plasmids at optimal concentrations resulted in greater than additive CAT activity from the JCVL promoter. This synergism suggests that the two activator proteins utilize alternative mechanisms to exert their effects. Using deletion mutations from the 5' end of the JCVL promoter, we demonstrated that different regions within the JCV enhancer/promoter are important for T-antigen and tat induction, implying that these activators function through distinct targets to increase JCVL promoter activity.

Antigens, Polyomavirus Transforming↗
PubMed1989

Regulation of JCVL promoter function: transactivation of JCVL promoter by JCV and SV40 early proteins.

To better understand the basis of cell type specificity of JCV replication, we have analyzed the expression of the viral late promoter in glial cells. Using transient transfection procedures, we show that the late gene expression, like that of the early gene, is restricted to glial cells. However, cotransfection with a plasmid producing the JCV early protein, T-antigen, stimulates expression from the JCV late promoter in both glial and non-glial cells. The SV40-encoded T-antigen acts similarly on transcription of JCV late promoter in both cell types. This transacting effect occurs at the level of RNA synthesis, as measured by the rate of transcription, stability of the message, and translation. These results indicate that basal JCV late promoter activity is restricted to glial cells, whereas in the presence of viral early protein this promoter functions in both glial and non-glial cells.

Antigens, Polyomavirus Transforming↗
PubMed1989

Factors determining in-hospital or late survival after aortic valve replacement.

To ascertain incremental risk factors for in-hospital and late mortality of patients undergoing AVR with the bovine pericardial valve, multiple variables were analyzed in a group of 240 patients undergoing AVR between 1977 and 1983. Follow-up totaled 12,023 patient-months (mean, 52.7 +/- 1.7 patient-months) and was 100 percent complete. Univariate analysis of incremental risk factors for in-hospital mortality identified the following: age over 60 years (p = 0.015); and advanced preoperative NYHA class (p = 0.003). Multivariate analysis of risk factors for in-hospital mortality identified the following: age (p = 0.038); NYHA class (p = 0.018); and year of operation (p = 0.049). Incremental risk factors for late mortality were identified as age (p = 0.003), year of operation (p = 0.003), concomitant procedure (p = 0.047), and valvular lesion (regurgitation) (p = 0.053). Actuarial survival of patients (+/- SE) was 87 +/- 2 percent, 75 +/- 3 percent, and 61 +/- 5 percent at 2, 5, and 8.7 years, respectively. The actuarial survival of patients experiencing valve-related events was 62.6 +/- 10.1 percent at 8.7 years, compared to 55.4 +/- 7 percent for those who did not (p = 0.38).

Actuarial Analysis↗