Electrocardiographic case--a man with recurrent syncope and aborted sudden death.
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Aged↗
Biomedical subjects
R S Tan
Publications and source records attributed to R S Tan.
Prescribing antidepressants in general practice. Low dose tricyclic antidepressants are effective in treating major depression.
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Antidepressive Agents, Tricyclic↗
Congestive heart failure in elderly patients. The treatment goal is improved quality, not quantity, of life.
Primary care physicians who see elderly patients are likely to see cases of congestive heart failure, since this condition is typically the result of long-standing hypertension or coronary artery disease. Recognizing the condition in elderly patients may not be easy, though, because clinical signs can be distorted by accompanying symptoms. In this article, the authors discuss pathophysiologic, diagnostic, and pharmacokinetic issues. They also describe therapy with diuretics, angiotensin-converting enzyme inhibitors, and digoxin and outline special considerations in the elderly.
Aged↗
Identification of the lysyl oxidase gene as target of the antioncogenic transcription factor, IRF-1, and its possible role in tumor suppression.
The transcriptional activator IFN regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the IFN system. IRF-1 also manifests tumor suppressive activity, and its inactivation could contribute to the development of human hematopoietic malignancies. Here, we report the identification of the lysyl oxidase gene as a target gene of IRF-1. An IRF response element was identified in the lysyl oxidase gene promoter. We also demonstrate that the transformed phenotype of ras-expressing embryonic fibroblasts with a null mutation in the IRF-1 allele could be suppressed by the expression of the lysyl oxidase cDNA, implicating its potential role in tumor suppression. Thus, the regulation of the lysyl oxidase gene by IRF-1 could contribute to the multistep process of malignant transformation.
3T3 Cells↗
Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies.
BACKGROUND: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN-alpha and -beta) and type II (IFN-gamma) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2. The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1). RESULTS: We generated mice lacking p48 by gene targeting. We show that p48 plays an essential role in both type I and type II IFN responses; activation of IFN-inducible genes and establishment of the antiviral state by IFN-alpha or -gamma are both severely impaired, and ISRE-binding activities induced by both IFNs are absent in the p48-negative embryonic fibroblasts (EFs). Furthermore, we generated mice deficient for both p48 and IRF-1 and found that at least one IFN-inducible gene is dependent on both factors. CONCLUSIONS: p48 and IRF-1 do not perform redundant functions in the cell, but rather complement one another in both type I and II IFN responses.
Animals↗
Regulation of IFN-alpha/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta.
BACKGROUND: Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN-stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN-stimulated response elements) to activate IFN-inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3gamma) also binds to virus-inducible elements in the IFN-alpha/beta genes, suggesting a potential new role of p48 in IFN production. RESULTS: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus-inducible elements within the IFN-alpha/beta promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction. CONCLUSIONS: Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN-alpha/beta promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.
Animals↗
The effect of low dose lofepramine in depressed elderly patients in general medical wards.
A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.
Administration, Oral↗
Clinical and histological features of 'mechanic's hands' in a patient with antibodies to Jo-1--a case report.
The clinical and histological features of 'mechanic's hands' are described in a patient with polymyositis characterized serologically by antibodies to histidyl tRNA synthetase (Jo-1). Although described in the past in association with polymyositis, these distinctive cutaneous lesions have only recently been associated with the 'anti-synthetase syndrome'. It is becoming apparent that recognition of subsets within the spectrum of polymyositis/dermatomyositis characterized by certain clinical and serological features not only have prognostic significance, but also may provide insights into mechanisms of disease.
Aged↗
Molecular analysis of hypoxanthine phosphoribosyl transferase mutants induced by glycidyl 1-naphthyl ether in mouse spleen cells in vivo.
Treatment of C57BL/6J mice with an epoxide, glycidyl 1-naphthyl ether (GNE), resulted in an average of a 3.4-fold increase in frequency of 6-thioguanine-resistant mutants of mouse spleen T-lymphocytes. In similar experiments with the epoxide trichloropropylene oxide, no increase in mutant frequency was found. To determine the kind and location of mutations in the coding region of the hypoxanthine phosphoribosyl transferase (HPRT) gene, 26 GNE-induced mutants and 17 spontaneous mutants were analyzed by direct sequencing of polymerase chain reaction amplified cDNA. Among the GNE-induced mutants, HPRT cDNA was present in 22, while that from 4 could not be detected. Among the spontaneous mutants, HPRT cDNA was present in 15 and absent in 2. Among GNE-induced mutants, base substitution in HPRT occurred in 15 of 22 mutants analyzed. Nine of 15 base substitutions involved TA base pairs, primarily TA-->CG transitions. Base substitutions were found throughout exons 3-7 but 46% of substitutions were located in exon 3 and one frameshift mutation involving a GC base pair in exon 3 was also observed. Among the spontaneous mutants, base substitutions of HPRT occurred in 7 of 15 mutants analyzed with 6 of 7 base substitutions involving a TA base pair and another 2 of the 15 mutants showed a 4 base pair deletion. The base substitution spectrum in GNE-induced mutants was different from that of the spontaneous mutants.
Amino Acid Sequence↗
Oral presentation of lymphoma: case report of T-cell lymphoma masquerading as oral Crohn's disease, and review of the literature.
A 15-year-old male with labial swelling, mouth ulcers and mucosal tags is reported. While the features were clinically consistent with oral Crohn's disease the patient proved to have a fatal T-cell lymphocytic lymphoma.
Adolescent↗
Chromatographic purification and characterization of EBV DNase from chemically induced lymphoid cells.
Epstein-Barr virus-associated deoxyribonuclease (EBV-DNase) was purified to homogeneity, as determined by silver staining, sequential column chromatography, and FPLC from Raji and P3HR-1 cells treated with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This viral protein was immunogenic and elicited high neutralization titer sera in rabbits. By silver staining of SDS-PAGE, Western immunoblot, and radioimmunoprecipitation using NPC patient sera and both polyclonal and monoclonal antibodies, the EBV DNase was identified as a 58K protein. The potential presence of two EBV DNases was also discussed.
Butyrates↗
Papular lesions and cutaneous lupus erythematosus: a comparative clinical and histological study using monoclonal antibodies.
Skin biopsies from 13 patients with papular lesions thought to be cutaneous lupus erythematosus were analyzed by light microscopy, direct immunofluorescence and immunohistochemically and compared to 22 biopsies from patients with discoid lupus, subacute cutaneous lupus erythematosus and acute cutaneous lesions of SLE. Papular lesions demonstrated fewer florid dermal and epidermal changes but a similar marked mononuclear cell infiltrate which in all groups was composed predominantly of T lymphocytes (68.4 +2- 11.2 SD) with the mean helper: suppressor (corrected Leu 3a:T8) ratio 1.73 +/- 0.60 SD. HLA-DR expression on keratinocytes was present in 20 patients, including 4 with papular lesions, and was strongly associated with liquefactive degeneration (chi 2, p less than 0.001), the hallmark of dermoepidermal junctional damage.
Antibodies, Antinuclear↗
Induction of virus enzymes by phorbol esters and n-butyrate in Epstein-Barr virus genome-carrying Raji cells.
Phorbol esters and n-butyrate (SB) together could induce Epstein-Barr virus (EBV) DNA polymerase and DNase activities in Raji cells (virus nonproducer). Neither 12-O-tetradecanoylphorbol-13-acetate (TPA) nor SB alone could induce these EBV enzyme activities, transcription of the EcoRI C-region or other EBV proteins in Raji cells. The enzyme induction caused by exposure of Raji cells to TPA-SB was the result of the synthesis of virus-specified RNA, and the increase of linear EBV DNA content in Raji cells caused by TPA alone was not sufficient for induction of EBV-enzyme activities. Temporal characteristics of the TPA-SB induction process, but not the phorbol 12,13-dibutyrate-SB induction process, in Raji cells were observed; a critical phase (10-24 h) postphorbol ester treatment in phorbol 12,13-dibutyrate-SB-treated Raji cells which was responsible for the synthesis of virus RNA and enzymes was found. Phospholipase C, which increases intracellular diacylglycerols (and subsequently activates protein kinase C) was able to partially substitute for TPA in the TPA-SB induction for EBV polymerase and DNase activities. Sphingosine, a protein kinase C inhibitor, partially prevented the induction of virus enzyme activities in Raji cells treated with phorbol 12,13-dibutyrate and SB. No apparent changes in the methylation state of EBV DNA (EcoRI C region) were observed when Raji cells were treated with SB and TPA, alone or in combination. These results suggest that induction of EBV polymerase and DNase activities by TPA-SB may involve protein kinase C activation and another factor triggered by SB which together increase transcription of EBV DNA.
Burkitt Lymphoma↗
Pagetoid reticulosis, epidermotropic mycosis fungoides and mycosis fungoides: a disease spectrum.
Using a standard technique involving monoclonal antibodies against T-cell subsets, we have shown that almost all the infiltrating T-cells in the epidermis of a patient with Pagetoid reticulosis (PR), one with epidermotropic mycosis fungoides (EMF) and one with poikiloderma atrophicans vasculare (PAV), were OKT8 positive (presumed cytotoxic/suppressor) T-cells. The infiltrating T-cells in the epidermis of a patient with limited plaque stage mycosis fungoides (MF), however, were almost exclusively Leu 3a-positive (presumed helper/inducer) T-cells as is usually found in this condition. The keratinocytes in the patients with PR, EMF and PAV were HLA-DR-positive whilst those in the patient with MF were HLA-DR-negative. We consider these four diseases to be part of the spectrum of mycosis fungoides, the first three conditions representing the early or benign end of the spectrum.
Adult↗
Association of Epstein-Barr virus early antigen diffuse component and virus-specified DNA polymerase activity.
The role of Epstein-Barr virus (EBV) early antigen diffuse component (EA-D) and its relationship with EBV DNA polymerase in EBV genome-carrying cells are unclear, EBV-specified DNA polymerase was purified in a sequential manner from Raji cells treated with phorbol-12,13-dibutyrate and n-butyrate by phosphocellulose, DEAE-cellulose, double-stranded DNA-cellulose, and blue Sepharose column chromatography. Four polypeptides with molecular masses of 110,000, 100,000, 55,000, and 49,000 daltons were found to be associated with EBV-specified DNA polymerase activity. A monoclonal antibody which could neutralize the EBV DNA polymerase activity was prepared and found to recognize 55,000- and 49,000-dalton polypeptides. An EA-D monoclonal antibody, R3 (G. R. Pearson, V. Vorman, B. Chase, T. Sculley, M. Hummel, and E. Kieff, J. Virol. 47:183-201, 1983), was also able to recognize these same two polypeptides associated with EBV DNA polymerase activity. It was concluded that EBV EA-D polypeptides, as identified by R3 monoclonal antibody, are critical components of EBV DNA polymerase.
Antibodies, Monoclonal↗
Milk recorder dermatitis.
Occupational contact dermatitis to Bronopol and Kathon CG has been identified in 3 milk recorders following the introduction of a new milk preservative. The source of exposure, sensitising potential and measures for prevention are discussed.
Adult↗
Demonstration of Epstein-Barr virus-specific DNA polymerase in chemically induced Raji cells and its antibody in serum from patients with nasopharyngeal carcinoma.
Epstein-Barr virus (EBV) has been found to be associated with nasopharyngeal carcinoma (NPC), and antibodies with high frequency and titer to EBV proteins have been found in sera from NPC patients. Raji cells, an EBV genome-carrying nonproducer cell line, treated with 12-O-tetradecanoylphorbol-13-acetate and n-butyrate induced a unique EBV DNA polymerase which has properties similar to the EBV DNA polymerase induced by 12-O-tetradecanoylphorbol-13-acetate in P3HR-1 cells, an EBV producer cell line. The possible presence of antibodies to this EBV DNA polymerase in NPC patient serum was examined. The mean number of EBV DNA polymerase units neutralized was 380 +/- 168 units/ml serum (mean +/- SD) in 48 sera from patients with NPC, whereas that in the sera from 52 healthy donors was 62 +/- 56 units/ml (p less than 0.01). The EBV DNA polymerase antibody was found to be associated with the immunoglobulin G but not the immunoglobulin A fraction, and its titer was not correlated with the titers against EBV DNase or virus capsid antigen-immunoglobulin A. Whether the EBV DNA polymerase antibody is against the EBV DNA polymerase core protein or its stimulating protein is still being investigated. This study demonstrated the high frequency and high titer of antibody against EBV DNA polymerase in serum from NPC patients and suggested the potential of utilizing this antibody titer to complement other methods for the early diagnosis or prognosis of NPC.
Antibodies, Viral↗
Biochemical markers of tumor diathesis and early cancer.
Many biochemical parameters have been used as tumor markers but few are satisfactory to reflect tumor diathesis and/or for early detection. Studies in the Cancer Institute, Chinese Academy of Medical Sciences, have indicated that serum alpha 1-acid glycoprotein and sialic acid were increased in lung cancers, but 20% of pulmonary tuberculosis patients were also positive. Serum polyamines determined by RIA were increased in cancer patients. The positive rates for cancer of lung and esophagus were 84% and 100%, respectively. Polyamine contents considerably increased in esophagus tissue of rats treated with methylbenzylnitrosamine, and this occurred far earlier than the tumor appeared. However, whether serum polyamine can be used for early detection of esophageal cancer awaits further studies. An unknown fluorescent compound in urine was found in normal people but was very much decreased in cancer patients. This compound showed cytostatic effect on tumor cells in vitro. Serum antibodies against EBV-associated DNase could be used as a marker for NPC.
Animals↗