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1.
Muscle Nerve ; 69(2): 157-165, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38018505

ABSTRACT

INTRODUCTION/AIMS: If myasthenia gravis (MG) symptoms are inadequately controlled, patients may experience exacerbations or life-threatening myasthenic crises. Patients with inadequately controlled MG symptoms tend to be treated with chronic intravenous immunoglobulin (IVIg) therapy and/or multiple immunosuppressant therapies (ISTs). This study aimed to examine disease burden, healthcare resource utilization, and associated costs in these patients. METHODS: This was a retrospective observational study using a claims database. Patients with MG were classified into three cohorts based on treatment over a 1-y follow-up period: (a) treated with four or more IVIg episodes (chronic IVIg cohort); (b) received two or more non-steroidal ISTs (NSISTs) sequentially (multiple NSIST cohort); (c) received neither chronic IVIg nor multiple NSISTs (reference cohort). Incidences of crises and exacerbations and annual healthcare costs in each cohort were estimated. RESULTS: In total, 3516 patients with MG were included in the analysis. Compared with the reference cohort (n = 2992), the MG crisis rate was approximately twice as high in both the chronic IVIg (n = 324) and multiple NSIST (n = 291) cohorts (p < 0.001); and the MG exacerbation rate was approximately four-fold higher in the chronic IVIg cohort (p < 0.001) and three-fold higher in the multiple NSIST cohort (p < 0.001). Median annual MG-related inflation-adjusted total healthcare costs were higher in the chronic IVIg ($81,900) and multiple NSIST ($30,300) cohorts than in the reference cohort ($2540). DISCUSSION: The burden of crises/exacerbations was substantially higher and healthcare costs were considerably greater in patients with MG treated with chronic IVIg or multiple NSISTs than in patients not receiving these treatments.


Subject(s)
Immunoglobulins, Intravenous , Myasthenia Gravis , Humans , United States/epidemiology , Immunoglobulins, Intravenous/therapeutic use , Myasthenia Gravis/drug therapy , Plasma Exchange , Health Care Costs , Immunosuppressive Agents , Cost of Illness
2.
Chemosphere ; 281: 130873, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34022596

ABSTRACT

Palm oil mill effluent (POME) is highly polluted wastewater that is to the environment if discharged directly to water source without proper treatment. Thus, a highly efficient treatment with reasonable cost is needed. This study reports the coagulation treatment of POME using integrated copperas and calcium hydroxide. The properties of copperas were determined using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), X-ray diffraction (XRD), and X-ray fluorescence (XRF). Coagulation was conducted using jar test experiments for various coagulant formulations and dosages (1000-5000 mg/L), initial pH (4-10), stirring speed (100-300 rpm), and sedimentation time (30-180 min). The characterisation results show that copperas has a compact gel network structure with strong O-H stretching and monoclinic crystal structure. The effectiveness of integrated copperas and calcium hydroxide (Ca(OH)2) with the formulation of 80:20 removed 77.6%, 73.4%, and 57.0% of turbidity, colour, and chemical oxygen demand (COD), respectively. Furthermore, the integration of copperas and Ca(OH)2 produced heavier flocs (ferric hydroxide), which improved gravity settling. The coagulation equilibrium analysis shows that the Langmuir model best described the anaerobic POME sample as the process exhibited monolayer adsorption. The results of this study show that copperas with the aid of Ca(OH)2 demonstrated high potential in the removal of those parameters from POME with acceptable final pH for discharge. The utilisation of this by-product as a coagulant in effluent treatment can unlock the potential of copperas for wider applications, improve its marketability, and reduce gypsum waste generation from the TiO2 industry.


Subject(s)
Industrial Waste , Waste Disposal, Fluid , Biological Oxygen Demand Analysis , Calcium Hydroxide , Industrial Waste/analysis , Palm Oil , Plant Oils
3.
Mymensingh Med J ; 29(2): 376-383, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32506093

ABSTRACT

Systemic lupus erythematosus (SLE) is a common autoimmune connective tissue disorder and mainly affected female patients. This cross sectional study was performed in the department of Cardiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2008 to June 2012. A total fifty (50) SLE patients were diagnosed on the basis of ACR criteria, having no cardiovascular symptoms. Another 50 age-matched normal individuals were included to compare with SLE group. Congenital vascular disease, ischaemic heart disease, congenital heart disease, rheumatic heart disease, hypothyroidism and any other inflammatory disease along with SLE were excluded from study. All patients were evaluated by Carotid duplex study. Mean age of SLE was 26.70±7.3 and mean age of normal subject was 25.64±8.01. Most of the SLE patients were female (about 92%) and male (about 8%). And about 94% was female in normal group and 6% was male. In Right common carotid arteries (RCCA), mean Intema medial thickness (IMT) was 0.86±0.10 IN SLE group and 0.73±0.06 in normal group. In LCCA, mean IMT was 0.89±0.14 in SLE group and 0.76±0.10 in normal group. IMT in SLE group was increased than control group. There was a significant difference (p=0.001) in both right and left side. The percentage rate of change in PSV and EDV of Carotid arteries of the SLE group was significantly higher than the control group (Both left and right side p=0.001). In RCCA, the PSV was 91.72±19.46 in SLE group and 62.60±6.66 in normal group (p=0.001). And EDV was 27.02±8.23 in SLE group and 16.48±2.32 in normal group (p=0.001). In LCCA, the PSV was 82.06±22.28 in SLE group and 60.36±7.54 in normal group (p=0.001). And EDV was 27.82±6.61 in SLE group and 18.08±2.69 in normal group (p=0.001). In LICA, mean PSV was 83.46±23.54 in SLE group and 60.36±7.54 in normal group (p=0.001). And EDV was 29.36±8.56 in SLE group and 18.08±2.69 in normal group (p=0.001). In RICA, mean PSV was 61.56±7.66 in SLE group and 62.16±5.35 in normal group (p=0.651) which was not significant. And EDV was 26.36±2.26 in SLE group and 19.00±2.17 in normal group (p=0.001). But majority of the vessels showed significant P value which signifies that vascular changes were more evident in SLE group than normal control group. SLE patients with carotid artery blood flow velocity and structural changes in endothelial function changes more evident than control group. Compared with the normal control group, IMT, PSV and EDV were significantly higher in SLE group, the difference was statistically significant (P<0.05). Vascular changes are common in SLE when clinically asymptomatic. Carotid duplex study is a non invasive tool for early detection of vascular changes to prevent stroke in SLE patients.


Subject(s)
Carotid Arteries , Lupus Erythematosus, Systemic , Bangladesh , Blood Flow Velocity , Cross-Sectional Studies , Female , Humans , Male
4.
Malays Orthop J ; 13(1): 36-41, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31001382

ABSTRACT

Introduction: Tibia is the most common long bone fractured due its vulnerable subcutaneous location and most often associated with acquired complications of delayed union or non-union due to infection. Amongst the various treatment options to treat them, the Ilizarov external fixator application is considered superior due to its multiple advantages. The objective of this study was to analyse the role of Ilizarov fixation in infected tibial non-union, as well as to assess bony union and associated functional outcomes. Materials and Methods: A retrospective review was conducted for the duration between 1st January 2005 to 31st December 2016. Total of fifty-one patients with tibial non-union associated with infection who treated with the Ilizarov fixator were included in the study. Patient records were reviewed for union of bone, bone and functional outcomes and complications. Results: The most common organism for infection was identified to be Staphylococcus Aureus. At the time of final follow-up all patients had achieved union except two, one of whom had to undergo amputation due to non-union and sepsis. Majority of the patients had an excellent score as per ASAMI grading system for bone and function results. The most common complication noted was pin track infections. Conclusion: In our experience, Ilizarov external fixator is better suited for infected non-union of tibia because it can provide a stable mechanical environment, bone transport, correct deformities, and enable weight bearing and hence we recommend its use for the same.

5.
Mymensingh Med J ; 27(2): 298-303, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29769494

ABSTRACT

This study was done to evaluate the clinical profile, management and to analysis of pregnancy outcomes of peripartum cardiomyopathy pregnant women. Follow up was done after treatment and to see the prognosis. All patients admitted with peripartum cardiomyopathy from July 2009 to June 2014 in the department of Cardiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh were considered for this observational study. Seventy two (72) women were evaluated. Primi-paras are 28 (39%) of the total study population. Fifty two patients (72%) were clinically improved and in 35 (48% ) the left ventricular functional status returned to normal with the treatment of Diuretics, selective Beta-blocker, Angiotensin converting enzyme inhibitor(ACEI) or Angiotensin receptor blocker (ARB) and vitamin B complex. Eleven cases (15%) developed persistent cardiomyopathy that is persistent left ventricular dysfunction beyond six months of presentation. Ten women (14%) presented with thromboembolic events and anti coagulant were prescribed for life long for secondary prevention. Maternal mortality was 8 (13%). Among all live births four had intra uterine growth retardation and another three had died during the neonatal period. The patients of peripartum cardiomyopathy were improved symptomatically and prognosis was good with the treatment of diuretic, selective beta-blocker, ACEI or ARB and vitamin B complex. Regular clinical follow up with echocardiography and monitoring of INR if the patients are in Anticoagulant are advised to reduce the morbidity and mortality.


Subject(s)
Cardiomyopathies , Pregnancy Complications, Cardiovascular , Puerperal Disorders , Bangladesh , Cardiomyopathies/therapy , Female , Humans , Peripartum Period , Pregnancy , Pregnancy Complications, Cardiovascular/therapy , Puerperal Disorders/therapy
6.
Oncogene ; 34(8): 1064-72, 2015 Feb 19.
Article in English | MEDLINE | ID: mdl-24632607

ABSTRACT

Glioblastomas (GBM) are highly radioresistant and lethal brain tumors. Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are a risk factor for the development of GBM. In this study, we systematically examined the contribution of IR-induced DSBs to GBM development using transgenic mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf and/or PTEN. Using low linear energy transfer (LET) X-rays to generate simple breaks or high LET HZE particles (Fe ions) to generate complex breaks, we found that DSBs induce high-grade gliomas in these mice which, otherwise, do not develop gliomas spontaneously. Loss of Ink4a and Arf was sufficient to trigger IR-induced glioma development but additional loss of Ink4b significantly increased tumor incidence. We analyzed IR-induced tumors for copy number alterations to identify oncogenic changes that were generated and selected for as a consequence of stochastic DSB events. We found Met amplification to be the most significant oncogenic event in these radiation-induced gliomas. Importantly, Met activation resulted in the expression of Sox2, a GBM cancer stem cell marker, and was obligatory for tumor formation. In sum, these results indicate that radiation-induced DSBs cooperate with loss of Ink4 and Arf tumor suppressors to generate high-grade gliomas that are commonly driven by Met amplification and activation.


Subject(s)
Brain Neoplasms/genetics , Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Breaks, Double-Stranded , Glioblastoma/genetics , Proto-Oncogene Proteins c-met/genetics , Animals , DNA Breaks, Double-Stranded/radiation effects , Gene Amplification , Gene Deletion , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Nude , Radiation, Ionizing
7.
Oncogene ; 34(1): 129-134, 2015 Jan 02.
Article in English | MEDLINE | ID: mdl-24362532

ABSTRACT

Epidermal growth factor receptor (EGFR)vIII is the most common EGFR mutant found in glioblastoma (GBM). EGFRvIII does not bind ligand, is highly oncogenic and is usually coexpressed with EGFR wild type (EGFRwt). EGFRvIII activates Met, and Met contributes to EGFRvIII-mediated oncogenicity and resistance to treatment. Here, we report that addition of EGF results in a rapid loss of EGFRvIII-driven Met phosphorylation in glioma cells. Met is associated with EGFRvIII in a physical complex. Addition of EGF results in a dissociation of the EGFRvIII-Met complex with a concomitant loss of Met phosphorylation. Consistent with the abrogation of Met activation, addition of EGF results in the inhibition of EGFRvIII-mediated resistance to chemotherapy. Thus, our study suggests that ligand in the milieu of EGFRvIII-expressing GBM cells is likely to influence the EGFRvIII-Met interaction and resistance to treatment, and highlights a novel antagonistic interaction between EGFRwt and EGFRvIII in glioma cells.


Subject(s)
Brain Neoplasms/metabolism , ErbB Receptors/metabolism , Gene Expression Regulation, Neoplastic , Glioblastoma/metabolism , Proto-Oncogene Proteins c-met/metabolism , Brain Neoplasms/drug therapy , Cell Line, Tumor , Dacarbazine/analogs & derivatives , Dacarbazine/chemistry , Epidermal Growth Factor/metabolism , Glioblastoma/drug therapy , Humans , Phenotype , Phosphorylation , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Temozolomide
8.
Oncogene ; 33(33): 4253-64, 2014 Aug 14.
Article in English | MEDLINE | ID: mdl-24077285

ABSTRACT

EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in-frame deletion in the extracellular domain of EGFR, does not bind ligand and is thought to be constitutively active. Although EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood. Here we present a new model of EGFRvIII activation and propose that oncogenic activation of EGFRvIII in glioma cells is driven by co-expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a striking increase in EGFRvIII tyrosine phosphorylation and activation while silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB-EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this study, we show that HB-EGF is induced by EGFRvIII only when EGFRwt is present. Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed-forward loop regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking inhibition of EGFRvIII-induced tumorigenicity, while increasing EGFRwt or HB-EGF levels resulted in accelerated EGFRvIII-mediated oncogenicity in an orthotopic mouse model. Furthermore, we demonstrate the existence of this loop in human GBM. Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely maintained by a continuous EGFRwt-EGFRvIII-HB-EGF loop, potentially an attractive target for therapeutic intervention.


Subject(s)
Brain Neoplasms/metabolism , ErbB Receptors/metabolism , Glioblastoma/metabolism , Intercellular Signaling Peptides and Proteins/physiology , Animals , Cell Line, Tumor , ErbB Receptors/genetics , Feedback, Physiological , Gene Expression Regulation, Neoplastic , Heparin-binding EGF-like Growth Factor , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Phosphorylation , Protein Multimerization , Protein Processing, Post-Translational , Transcriptional Activation
9.
Cell Death Differ ; 15(2): 344-53, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18007664

ABSTRACT

There is considerable interest in understanding how inflammatory responses influence cell proliferation and cancer. In this study, we show that the receptor-interacting protein (RIP1), a critical mediator of inflammation and stress-induced NF-kappaB activation, regulates the expression of the epidermal growth factor receptor (EGFR). Mouse embryo fibroblasts (MEFs) derived from RIP1 knockout mice express very high levels of the EGFR. Reconstitution of RIP1(-/-) MEFs with RIP1 results in a lowering of EGFR levels. RIP1 influences EGFR at the mRNA level by regulating the EGFR promoter. Expression of RIP1 inhibits the EGFR promoter. RIP1 downregulates EGFR expression by interfering with the function of Sp1, which is a key activator of EGFR transcription. RIP1 suppresses Sp1 activity and overexpression of Sp1 reverses RIP1-mediated repression of the EGFR promoter. RIP1 is present both in the cytoplasm and in the nucleus. RIP1 coimmunoprecipitates with Sp1 in vivo and binds directly to Sp1 in vitro. A RIP1 mutant lacking the death domain fails to suppress Sp1 activity and the EGFR promoter, suggesting a critical role for the RIP1 death domain in EGFR regulation. Thus, our study identifies a new link between inflammatory and growth factor signaling pathways mediated by RIP1 and provides insight into the mechanism used by RIP1 to regulate EGFR levels.


Subject(s)
ErbB Receptors/metabolism , NF-kappa B/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Sp1 Transcription Factor/metabolism , Animals , Cell Line, Tumor , Cell Nucleus/metabolism , DNA/metabolism , Down-Regulation , ErbB Receptors/genetics , Humans , Mice , Mice, Knockout , Promoter Regions, Genetic , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Recombinant Proteins/metabolism , Sp1 Transcription Factor/antagonists & inhibitors
10.
J Pak Med Assoc ; 52(3): 111-6, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12071065

ABSTRACT

OBJECTIVE: Brain abscess carries significant morbidity and mortality. Our objective was to elucidate the clinical presentation of brain abscess and to assess predictors of mortality in these patients. METHODS: All patients with a brain abscess presenting to the Aga Khan University Hospital, a tertiary care referral center in Karachi, Pakistan, were studied retrospectively. Statistical analysis involved univariate analysis and a logistic regression model. RESULTS: Among the 66 patients analyzed, a distant metastatic focus of infection was the most commonly identified predisposing factor (29%). Otogenic infection was the commonest contiguous source and sinusitis was noticeably absent. Multiple abscesses were frequent (35%). Streptococci were the most common isolates (39%). Lumbar puncture was performed in 44% and steroids administered in 33%. Treatment was surgical in 58%. Most comatose patients were treated conservatively. Overall mortality was 29%. Univariate analysis identified comatose presentation and identification of a distant focus of infection as predictors of mortality. The logistic regression model, however, identified a distant focus of infection as the only independent predictor. CONCLUSION: Age greater than 30 years, corticosteroid use, multiple abscesses, performance of lumbar puncture and conservative management had no affect on outcome.


Subject(s)
Brain Abscess/mortality , Brain Abscess/therapy , Adolescent , Adult , Aged , Brain Abscess/diagnosis , Child , Child, Preschool , Combined Modality Therapy , Developing Countries , Female , Humans , Incidence , Magnetic Resonance Imaging , Male , Middle Aged , Pakistan/epidemiology , Predictive Value of Tests , Prognosis , Risk Factors , Severity of Illness Index , Survival Analysis , Tomography, X-Ray Computed
12.
FEBS Lett ; 491(1-2): 9-15, 2001 Feb 23.
Article in English | MEDLINE | ID: mdl-11226409

ABSTRACT

Previous studies have shown that certain tumor cell lines which naturally express high levels of the epidermal growth factor receptor (EGFR) undergo apoptosis when exposed to epidermal growth factor. Whether this phenomenon is a direct result of receptor overexpression or some other genetic alteration renders these cells sensitive to apoptosis is yet to be established. We show that experimentally increasing the level of EGFR expression predictably leads to apoptosis in a variety of cell types which requires an active tyrosine kinase but not EGFR autophosphorylation sites. Expression of a dominant negative Ras mutant in EGFR overexpressing cells results in a significant potentiation of EGFR induced apoptosis suggesting that Ras activation is a key survival signal generated by the EGFR. We propose that potentiation of EGFR induced apoptosis by dominant negative Ras results, at least in part, by a block of Akt activation.


Subject(s)
Apoptosis , Epidermal Growth Factor/metabolism , ErbB Receptors/genetics , Protein Serine-Threonine Kinases , Proto-Oncogene Proteins p21(ras)/genetics , Blotting, Western , ErbB Receptors/metabolism , Genes, Dominant , Humans , Mutation , Phosphorylation , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-akt , Proto-Oncogene Proteins p21(ras)/metabolism , Signal Transduction , Tumor Cells, Cultured
13.
J Biol Chem ; 276(12): 8865-74, 2001 Mar 23.
Article in English | MEDLINE | ID: mdl-11116146

ABSTRACT

The transcription factor nuclear factor-kappaB (NF-kappaB) is activated by a diverse number of stimuli including tumor necrosis factor-alpha, interleukin-1, UV irradiation, viruses, as well as receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR). NF-kappaB activation by the tumor necrosis factor receptor (TNFR) involves the formation of a multiprotein complex termed a signalosome. Although previous studies have shown that the activated EGFR can induce NF-kappaB, the mechanism of this activation remains unknown. In this study, we identify components of the signalosome formed by the activated EGFR required to activate NF-kappaB and show that, although the activated EGFR uses mechanisms similar to the TNFR, it recruits a distinct signalosome. We show the EGFR forms a complex with a TNFR-interacting protein (RIP), which plays a key role in TNFR-induced NF-kappaB activation, but not with TRADD, an adaptor protein which serves to recruit RIP to the TNFR. Furthermore, we show that the EGFR associates with NF-kappaB-inducing kinase (NIK) and provide evidence suggesting multiprotein complex formation between the EGFR, RIP, and NIK. Using a dominant negative NIK mutant, we show that NIK activation is required for EGFR-mediated NF-kappaB induction. We also show that a S32/36 IkappaBalpha mutant blocks EGFR-induced NF-kappaB activation. Our studies also suggest that a high level of EGFR expression, a frequent occurrence in human tumors, is optimal for epidermal growth factor-induced NF-kappaB activation. Finally, although protein kinase B/Akt has been implicated in tumor necrosis factor and PDGF-induced NF-kappaB activation, our studies do not support a role for this protein in EGFR-induced NF-kappaB activation.


Subject(s)
ErbB Receptors/physiology , I-kappa B Proteins , NF-kappa B/metabolism , Protein Serine-Threonine Kinases/physiology , Proteins/physiology , Base Sequence , Cell Line , DNA Primers , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , Mutation , NF-KappaB Inhibitor alpha , Protein Binding , Protein Serine-Threonine Kinases/metabolism , Proteins/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases , NF-kappaB-Inducing Kinase
14.
Oncogene ; 16(12): 1525-31, 1998 Mar 26.
Article in English | MEDLINE | ID: mdl-9569019

ABSTRACT

The Oligodendrocyte-Myelin glycoprotein gene (OMgp) is placed within an intron of the NF1 gene. Neurofibromin, the product of NF1, acts as a RasGAP and suppresses growth; inactivating mutations in NF1 lead to neurofibromatosis type 1. We report that OMgp also has growth suppressive effects and downregulates mitogenic signaling pathways closely related to those influenced by neurofibromin. Overexpression of OMgp alters mitogenic signaling in NIH3T3 fibroblasts. Cells overexpressing OMgp grow more slowly in serum compared to controls and show a partial G1 block upon cell cycle analysis. PDGF is the primary mitogen for fibroblasts in serum. Overexpression of OMgp alters PDGF signaling in fibroblasts which results in a block of mitogenic signaling. PDGF induced activation of c-Src is blocked, as is the induction of c-Myc and c-Fos, while tyrosine phosphorylation of the PDGFbeta receptor, PLCgamma1 and induction of c-Jun are intact. Although a number of genes embedded within other genes have been described, the biological significance of this arrangement remains unknown. We demonstrate here that structurally unrelated products of two such genes may exercise closely related functions. Our data also raise the possibility of a role for OMgp in disorders of cell proliferation such as NF1.


Subject(s)
Genes, Neurofibromatosis 1 , Growth Inhibitors/genetics , Myelin-Associated Glycoprotein/genetics , Proteins/genetics , 3T3 Cells , Animals , CSK Tyrosine-Protein Kinase , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cell Cycle/genetics , Cell Division/genetics , Enzyme Activation , GPI-Linked Proteins , Gene Expression Regulation, Neoplastic , Genes, Immediate-Early/genetics , Mice , Mitogen-Activated Protein Kinases/metabolism , Myelin Proteins , Myelin-Associated Glycoprotein/biosynthesis , Myelin-Oligodendrocyte Glycoprotein , Nerve Tissue Proteins/metabolism , Neurofibromin 1 , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Receptor, Platelet-Derived Growth Factor beta , Receptors, Platelet-Derived Growth Factor/metabolism , Receptors, Platelet-Derived Growth Factor/physiology , Transfection , Tyrosine/metabolism , src-Family Kinases
15.
J Biol Chem ; 273(12): 6885-91, 1998 Mar 20.
Article in English | MEDLINE | ID: mdl-9506992

ABSTRACT

Receptor tyrosine kinases are classified into subfamilies, which are believed to function independently, with heterodimerization occurring only within the same subfamily. In this study, we present evidence suggesting a direct interaction between the epidermal growth factor (EGF) receptor (EGFR) and the platelet-derived growth factor beta (PDGFbeta) receptor (PDGFbetaR), members of different receptor tyrosine kinase subfamilies. We find that the addition of EGF to COS-7 cells and to human foreskin Hs27 fibroblasts results in a rapid tyrosine phosphorylation of the PDGFbetaR and results in the recruitment of phosphatidylinositol 3-kinase to the PDGFbetaR. In R1hER cells, which overexpress the EGFR, we find ligand-independent tyrosine phosphorylation of the PDGFbetaR and the constitutive binding of a substantial amount of PI-3 kinase activity to it, mimicking the effect of ligand in untransfected cells. In support of the possibility that this may be a direct interaction, we show that the two receptors can be coimmunoprecipitated from untransfected Hs27 fibroblasts and from COS-7 cells. This association can be reconstituted by introducing the two receptors into 293 EBNA cells. The EGFR/PDGFbetaR association is ligand-independent in all cell lines tested. We also demonstrate that the fraction of PDGFbetaR bound to the EGFR in R1hER cells undergoes an EGF-induced mobility shift on Western blots indicative of phosphorylation. Our findings indicate that direct interactions between receptor tyrosine kinases classified under different subfamilies may be more widespread than previously believed.


Subject(s)
ErbB Receptors/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Receptors, Platelet-Derived Growth Factor/metabolism , Animals , COS Cells , Cell Line , Humans , Precipitin Tests , Protein Binding , Receptor, Platelet-Derived Growth Factor beta , Signal Transduction , Transfection
16.
J Neurochem ; 70(4): 1704-11, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9523589

ABSTRACT

The oligodendrocyte-myelin glycoprotein (OMgp) is a 110-kDa glycosylphosphatidylinositol-linked protein that was initially identified as a myelin-specific protein but whose precise function remains unknown. In this study, immunohistochemistry, western blots, in situ hybridization, and northern blots were used to determine the distribution of OMgp in the mouse brain. OMgp is present in a concentration detectable on western blots in the brains of newborn mice, and its concentration gradually increases until day 24 of life. OMgp mRNA is also present in amounts detectable on northern blots in the brains of newborn mice, and its concentration gradually increases until day 21 of life, after which the concentration diminishes a little. Most of the OMgp in the mouse brain appears to be expressed in diverse groups of neurons, but it is particularly prominent in large projection neurons such as the pyramidal cells of the hippocampus, the Purkinje cells of the cerebellum, motoneurons in the brainstem, and anterior horn cells of the spinal cord. However, OMgp is not confined to these cells and is expressed in cells in the white matter as well. The OMgp gene is placed within an intron of the neurofibromatosis type I gene and on the opposite strand. This organization raises the possibility that there may be a relationship between the functions of the products of the two genes. In support of this possibility, we show that within the mouse CNS OMgp and neurofibromin are expressed in the same cell types.


Subject(s)
Central Nervous System/metabolism , Mice/metabolism , Myelin-Associated Glycoprotein/metabolism , Neurons/metabolism , Aging/metabolism , Animals , Animals, Newborn/growth & development , Animals, Newborn/metabolism , Central Nervous System/cytology , GPI-Linked Proteins , Humans , Immunohistochemistry , In Situ Hybridization , Mice, Inbred BALB C , Myelin Proteins , Myelin-Oligodendrocyte Glycoprotein , Neurofibromin 1 , Proteins/metabolism
17.
J Assoc Off Anal Chem ; 67(5): 939-41, 1984.
Article in English | MEDLINE | ID: mdl-6501159

ABSTRACT

Santonin gives a characteristic alkaline vs acidic difference spectrum. This was used for its estimation in pharmaceuticals and in the crude drug. Santonin was first extracted and purified through a specific partition procedure; then the difference absorbance was measured either at the maximum, 285 nm, or the minimum, 242 nm. The percentage of santonin can be calculated either by reference to the difference absorbance of a reference santonin sample, treated similarly, or by making use of the determined absorptivity. Measurement at the maximum is advisable, especially when the crude drug is assayed, because natural contaminants may interfere with the difference absorbance at the minimum.


Subject(s)
Plants, Medicinal/analysis , Santonin/analysis , Chemical Phenomena , Chemistry , Spectrophotometry, Infrared/methods
18.
Planta Med ; 43(11): 290-2, 1981 Nov.
Article in English | MEDLINE | ID: mdl-17402047

ABSTRACT

Otosenine and senecionine/seneciphyllme were isolated from Senecio aegyptius and S. desfontainei, respectively. Senecionine and seneciphylline easily cocrystallize; m.p. and IR-spectra of mixtures of both alkaloids and their separation by PC are described. IR evidence of individual alkaloids and of the alkaloid-pair are shown.

19.
J Nat Prod ; 43(4): 452-8, 1980.
Article in English | MEDLINE | ID: mdl-7431023

ABSTRACT

A spectrophotometric method is presented for assaying Senna and its preparations, for both total sennosides and total rhein glycosides content. The method ensures complete elimination of other minor non-carboxylic anthracene derivatives, as well as flavonoidal contaminants. The proposed method quantitates the actual total sennosides content, through the elimination of these contaminants, and through correction for the interference due to the coexistence of rhein with sennidins, in the final determinative step. This would eliminate false high figures for total sennosides by earlier procedures and reflects, perspectively, the actual potency of the assayed samples.


Subject(s)
Anthraquinones/analysis , Glycosides/analysis , Senna Extract/analysis , Glucosides/analysis , Sennosides , Spectrophotometry/methods , Tablets/analysis
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