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Dual activity of pyrrolidine dithiocarbamate on kappaB-dependent gene expression in U937 cells: II. Regulation by tumour necrosis factor-alpha.

In the human promonocytic U937 cell line, pyrrolidine dithiocarbamate (PDTC) was a potent inhibitor of the nuclear factor-kappaB (NF-kappaB) signalling pathway induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). However, PDTC did not inhibit tumour necrosis factor-alpha (TNF-alpha)-induced NF-kappaB DNA binding activity but potentiated the effect of TNF-alpha on kappaB-dependent gene expression. The stimulatory effect of PDTC with TNF-alpha was not observed with an HIV-1 LTR reporter construct containing two mutated kappaB binding sites or with a construct with a mutation

The zinc finger-containing transcription factor Gata-4 is expressed in the developing endocrine pancreas and activates glucagon gene expression.

Gene inactivation studies have shown that members of the Gata family of transcription factors are critical for endoderm development throughout evolution. We show here that Gata-4 and/or Gata-6 are not only expressed in the adult exocrine pancreas but also in glucagonoma and insulinoma cell lines, whereas Gata-5 is restricted to the exocrine pancreas. During pancreas development, Gata-4 is expressed already at embryonic d 10.5 and colocalizes with early glucagon+ cells at embryonic d 12.5. Gata-4 was able to transactivate the glucagon gene both in heterologous BHK-21 (nonislet Syrian baby hamst

The ARP-1 orphan receptor represses steroid-mediated stimulation of human placental lactogen gene expression.

Studies were performed to determine whether ARP-1, which is an orphan receptor of the steroid receptor superfamily, inhibits basal activity of the human placental lactogen (hPL) promoter and the increase in hPL promoter activity in response to the receptors for thyroid hormone (TR) and retinoic acid (RAR). Co-transfection of an ARP-1 expression vector into BeWo choriocarcinoma cells, along with an expression vector containing 1.2 kb of the hPL promoter coupled to a CAT reporter gene, resulted in a dose-dependent inhibition of basal CAT activity. In addition, ARP-1 inhibited the stimulation of

The EBNA-2 arginine-glycine domain is critical but not essential for B-lymphocyte growth transformation; the rest of region 3 lacks essential interactive domains.

Since deletion of region 3 (amino acids [aa] 333 to 425) of Epstein-Barr virus nuclear protein 2 (EBNA-2) results in EBV recombinants which cannot transform primary B lymphocytes (J. I. Cohen, F. Wang, and E. Kieff, J. Virol. 65:2545-2554, 1991), the role of domains of region 3 was investigated. Deletion of the Arg-Gly repeat domain, R-337GQSRGRGRGRGRGRGKG354, results in EBV recombinants that transform primary B lymphocytes with modestly decreased activity. The transformed cells grow slowly and are difficult to expand. EBNA-2 deleted for the Arg-Gly domain does not associate with the nuclear c

p11 expression in human bronchial epithelial cells is increased by nitric oxide in a cGMP-dependent pathway involving protein kinase G activation.

The effect of nitric oxide on p11 expression was studied in an immortalized human bronchial epithelial cell line (BEAS-2B cells). Three nitric oxide donors were used: spermine NONOate (SP), (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), and S-nitrosoglutathione (SNOG). All three nitric oxide donors had similar effects resulting in dose-dependent and time-dependent accumulation of p11 protein and an increase of steady-state p11 mRNA. Studies using a reporter gene containing the region from -1499 to +89 of the p11 promoter demonstrated an increase in transcriptional activity after stimulation wit

The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal.

The Gfi-1 proto-oncogene is activated by provirus insertion in T-cell lymphoma lines selected for interleukin-2 (IL-2) independence in culture and in primary retrovirus-induced thymomas and encodes a nuclear, sequence-specific DNA-binding protein. Here we show that Gfi-1 is a position- and orientation-independent active transcriptional repressor, whose activity depends on a 20-amino-acid N-terminal repressor domain, coincident with a nuclear localization motif. The sequence of the Gfi-1 repressor domain is related to the sequence of the repressor domain of Gfi-1B, a Gfi-1-related protein, and

Varicella-zoster virus open reading frame 61 protein is functionally homologous to herpes simplex virus type 1 ICP0.

The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is thought to be the homolog of herpes simplex virus type 1 (HSV-1) ICP0, based on gene location and limited amino acid homology. However, HSV-1 ICP0 trans activates HSV-1 genes, while VZV ORF61 protein trans represses the function of VZV trans activators on VZV promoters in transient expression assays. To investigate the functional relatedness of HSV-1 ICP0 and VZV ORF61 protein, we established Vero and MeWo cell lines which stably express VZV ORF61 under the control of a metallothionein promoter and performed complementat

Prospective study evaluating the incidence of bacteraemia and bacteruria in afebrile and febrile neutropaenic dogs undergoing chemotherapy.

The purpose of this prospective study was to determine the incidence and character of bacteraemia and bacteruria in afebrile and febrile neutropaenic dogs undergoing cytotoxic chemotherapy. Fifty-five neutropaenic dogs presenting to the University of Wisconsin Veterinary Medical Teaching Hospital were enrolled for a total of 57 neutropaenic episodes. The overall incidence of bacteraemia was 12.3% (n = 7/57). Three afebrile dogs and four febrile dogs were bacteraemic; this difference was not significant (P = 0.6968). The overall incidence of bacteruria was 7.5% (n = 4/53). Two afebrile dogs and

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… The S. pseudintermedius infection (febrile group) was resistant to all antibiotics tested (chloramphenicol, ciprofloxacin, clindamycin, erythromycin, gentamicin, minocycline, tetracycline, penicillin and TMS) except amikacin and oxacillin. … The Staphylococcus pseudintermedius was multi‐drug–resistant including resistance to chloramphenicol, ciprofloxacin, clindamycin, erythromycin, gentamicin, minocycline, tetracycline, penicillin and TMS, with susceptibility for oxacillin (and beta‐lactam agents) and amikacin. …

Treatment options for vancomycin-resistant enterococcal infections.

Serious infection with vancomycin-resistant enterococci (VRE) usually occurs in patients with significantly compromised host defences and serious co-morbidities, and this magnifies the importance of effective antimicrobial treatment. Assessments of antibacterial efficacy against VRE have been hampered by the lack of a comparator treatment arm(s), complex treatment requirements including surgery, and advanced illness-severity associated with a high crude mortality. Treatment options include available agents which don't have a specific VRE approval (chloramphenicol, doxycycline, high-dose ampici…

Роль кишечника микробиота-митохондрия в нейродегенерации: основополагающие механизмы и потенциальные методы лечения.

Появляющиеся данные свидетельствуют о том, что микробиота кишечника тесно связана с патологическими проявлениями множественных нейродегенеративных заболеваний через ось кишечника, которая относится к перекрестку между кишечником и центральной нервной системой. Еще важнее то, что митохондрия считается выдающимся посредником взаимодействия между кишечной микробиотой и мозгом. Кишечные микробы могут модифицировать функцию митохондриала в центральной нервной системе, чтобы повлиять на развитие нейродегенеративных заболеваний. Митохондрия необходима для удовлетворения значительных потребностей носи

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… The administration of chloramphenicol was found to effectively inhibit neurotoxins, such as MPTP and paraquat-induced PD pathology, and to significantly increase the activity of primary dopaminergic neurons from rat embryos. … The protective effect of chloramphenicol on neurons was mediated by targeting mitochondrial complex I and by the attenuation of ROS production; paraquat-induced dopaminergic neuron loss was associated with oxidative stress and ROS via regulating mitochondrial complex I (Han et al., 2019). …

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, i

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… . | Infantile Chloramphenicol | 25 mg/mL Oral solution | Alternative treatment of serious infections, by susceptible bacteria; Typhoid fever; Meningeal plague; Brazilian spotted fever and other rickettsiosis; Secondary infection by bothropic accident. | Infantile Clindamycin hydrochloride | 75 mg/5 mL … Presentations | Main Indication of Use | Average Price (USD) | Estimated Users | Average Treatment Time | Annual Cost Estimate (USD) Chloramphenicol 25 mg/mL Oral solution | Alternative treatment of serious infections, by susceptible bacteria; Typhoid fever; Meningeal plague; Brazilian spotted fever …

Acute interstitial nephritis - a reappraisal and update.

Acute interstitial nephritis (AIN) is an under recognized and under diagnosed cause of acute kidney injury (AKI). It is estimated to account for 15 - 20% of cases of AKI; it is the reported diagnosis in 2.8% of all kidney biopsies, and 13.5% of biopsies done specifically for acute renal failure. Considerable evidence implicates antigen initiated cell-mediated injury in the pathogenesis of AIN. Drugs account for 70% of all cases, with over 150 different agents incriminated. The remaining cases are due to infections, autoimmune diseases, and rarely idiopathic. The central component of renal inju

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… cases reported Methicillin, rifampin, ciprofloxacin Incidence < 30 cases reported Acyclovir, amoxicillin, ampicillin, atazanivir, carbenicillin, cefazolin, cefaclor, cefamandole, cefotaxime, cefotetan, cefoperazone, cefoxitin, ceftriaxone, cephalothin, cephalexin, cephradine, cephaloridine, cephapirin, chloramphenicol … cases reported Methicillin, rifampin, ciprofloxacin Incidence < 30 cases reported Acyclovir, amoxicillin, ampicillin, atazanivir, carbenicillin, cefazolin, cefaclor, cefamandole, cefotaxime, cefotetan, cefoperazone, cefoxitin, ceftriaxone, cephalothin, cephalexin, cephradine, cephaloridine, cephapirin, chloramphenicol …

Genomic structure and chromosomal mapping of the gene coding for ICBP90, a protein involved in the regulation of the topoisomerase IIalpha gene expression.

We have recently identified a novel CCAAT box binding protein (ICBP90) involved in the regulation of topoisomerase IIalpha gene expression. We have observed that it is expressed in non-tumoral proliferating human lung fibroblast cells whereas in HeLa cells, a tumoral cell line, ICBP90 was still present even when cells were at confluence. In the present study, we have determined the ICBP90 gene structure by screening of a human placenta genomic library and PCR analysis. We report that the ICBP90 gene spans about 35.8 kb and contains six coding exons named A to F. In the 5' upstream sequence of

Pentoxifylline promotes replication of human cytomegalovirus in vivo and in vitro.

OKT3 monoclonal antibody (MoAb) therapy is well established in the prevention and therapy of acute rejection in transplant patients. Unfortunately, this therapy is associated with several short-term (cytokine release syndrome) and long-term (infections, EBV-related lymphoma) side effects. Recently, we were able to demonstrate an association between the TNF alpha release following the first OKT3 MoAb infusions and the appearance of human cytomegalovirus (HCMV) reactivation several days later. In order to prevent this TNF alpha associated HCMV reactivation patients were additionally treated with

Positive and negative transcriptional control by the TAL1 helix-loop-helix protein.

Tumor-specific activation of the TAL1 gene is the most common genetic defect associated with T-cell acute lymphoblastic leukemia. The TAL1 gene products possess a basic helix-loop-helix (bHLH) motif, a protein-dimerization and DNA-binding domain found in several transcription factors. TAL1 polypeptides interact, in vitro and in vivo, with class A bHLH proteins (e.g., E47) to form heterodimers with sequence-specific DNA-binding activity. In this study, we show that TAL1 can regulate the transcription of an artificial reporter gene that contains binding sites for bHLH heterodimers involving TAL1

Leber Hereditary Optic Neuropathy With Magnetic Resonance Imaging Findings Suggestive of Optic Perineuritis and Optic Neuritis: A Diagnostic Challenge.

Leber hereditary optic neuropathy (LHON) is a rare mitochondrial disorder characterized by subacute, painless, and bilateral vision loss, typically affecting young men. LHON is caused by mitochondrial DNA mutations, most commonly m.11778G>A, m.14484T>C, and m.3460G>A. LHON has incomplete penetrance, with a higher prevalence in men, and its diagnosis is often delayed because of clinical overlap with other optic nerve disorders, such as optic neuritis. Herein, we report the case of a 37-year-old man presenting with progressive vision loss in both eyes over two months. Early magnetic resonance im

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… However, there was no evidence to suggest any potential contributing factors, such as nutritional deficiencies (including deficiencies of vitamins B1 and B12, folate, vitamin B6, or vitamin E), exposure to toxic substances (such as lead, methanol, ethylene glycol, chloramphenicol, digoxin, ethambutol …

Neisseria meningitidis Induced Fatal Waterhouse-Friderichsen Syndrome in a Patient Presenting With Disseminated Intravascular Coagulation and Multiple Organ Failure.

Neisseria meningitidis-induced acute systemic meningococcal disease is an emergency and a fatal condition that has a high mortality rate. In patients with a fulminant infection, a maculopapular petechial eruption, purpura fulminans, or an ecchymotic lesion are worrisome signs reflecting disseminated intravascular coagulation (DIC) and hint at Waterhouse-Friderichsen syndrome (WFS). Here, we describe a rare case of a patient with a fulminant Neisseria meningitidis-induced acute systemic meningococcal disease presenting with high-grade fever without meningitis symptoms. Fatal septicemia with DIC

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… If patient was intolerant or allergic to beta-lactam antibiotics, chloramphenicol was an acceptable alternative medication [ 16 ]. …

The SMN genes are subject to transcriptional regulation during cellular differentiation.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha-motor neurons and muscular atrophy. The causal survival motor neuron (SMN) gene maps to a complex region of chromosome 5q13 harbouring an inverted duplication. Thus, there are two SMN genes, SMN1 and SMN2, but SMN1-deficiency alone causes SMA. In this study we demonstrate, for the first time, down-regulation of SMN promoter activity during cellular differentiation. Specifically, the minimal SMN promoter is four times more active in undifferentiated embryonal carcinoma P19 cells compa

HIV-1 Nef alters the expression of betaII and epsilon isoforms of protein kinase C and the activation of the long terminal repeat promoter in human astrocytoma cells.

In the human immunodeficiency virus type 1 (HIV-1)-infected brain, the virus does not replicate in astrocytes, but a synthesis of viral regulatory proteins occurs in these cells, leading to accumulation of Nef. As an approach to understand the effects of Nef on astrocyte functional activity, we analyzed whether intracellular Nef interferes with the expression and activation of the enzyme protein kinase C (PKC), which is an important regulator of astroglial functions and HIV-1 replication. Astrocytoma clones (U251 MG) not expressing Nef (Neo), or expressing wild-type Nef (Bru) or nonmyristoylat

A truncated mutant (residues 58-140) of the hepatitis B virus X protein retains transactivation function.

The hepatitis B virus X protein (HBx) sequence (154 aa) has been divided into six regions (A-F) based on its sequence homology with X proteins of other mammalian hepadnaviruses. Regions A, C, and E are more conserved and include all the four conserved cysteines (C7, C61, C69, and C137). To localize the regions of HBx important for transactivation, a panel of 10 deletion mutants (X5-X14) and 4 single point mutants (X1-X4), each corresponding to a conserved cysteine residue, was constructed by site-directed mutagenesis. A HBx-specific monoclonal antibody was developed and used to confirm the exp