Generalized pustular psoriasis following a short course of cyclosporin (Neoral)
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Adult↗
Biomedical subjects
R Mahendran
Publications and source records attributed to R Mahendran.
Insertional editing of mitochondrial tRNAs of Physarum polycephalum and Didymium nigripes.
tRNAs encoded on the mitochondrial DNA of Physarum polycephalum and Didymium nigripes require insertional editing for their maturation. Editing consists of the specific insertion of a single cytidine or uridine relative to the mitochondrial DNA sequence encoding the tRNA. Editing sites are at 14 different locations in nine tRNAs. Cytidine insertion sites can be located in any of the four stems of the tRNA cloverleaf and usually create a G. C base pair. Uridine insertions have been identified in the T loop of tRNALys from Didymium and tRNAGlu from Physarum. In both tRNAs, the insertion creates the GUUC sequence, which is converted to GTPsiC (Psi = pseudouridine) in most tRNAs. This type of tRNA editing is different from other, previously described types of tRNA editing and resembles the mRNA and rRNA editing in Physarum and Didymium. Analogous tRNAs in Physarum and Didymium have editing sites at different locations, indicating that editing sites have been lost, gained, or both since the divergence of Physarum and Didymium. Although cDNAs derived from single tRNAs are generally fully edited, cDNAs derived from unprocessed polycistronic tRNA precursors often lack some of the editing site insertions. This enrichment of partially edited sequences in unprocessed tRNAs may indicate that editing is required for tRNA processing or at least that RNA editing occurs as an early event in tRNA synthesis.
Animals↗
Obsessional symptoms associated with risperidone treatment.
OBJECTIVE: The aim of this paper is to report the occurrence of obsessional symptoms with risperidone treatment in a patient with no past history of obsessive-compulsive symptoms. CLINICAL PICTURE: A 26-year-old, single, Chinese lady with a chronic untreated schizophrenic illness was prescribed risperidone after she experienced side effects with other antipsychotic medication. After the second week on risperidone, she developed obsessional symptoms. TREATMENT AND OUTCOME: The obsessional symptoms responded to treatment with low dose clomipramine. CONCLUSION: The potential for the newer antipsychotic medication to precipitate or exacerbate obsessive-compulsive symptoms during treatment for schizophrenia must be borne in mind.
Adult↗
Intraventricular tumor (astrocytoma) associated with an organic psychosis.
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Adult↗
Use of atypical neuroleptics in a state mental institute.
The authors sought to give a perspective of the local use of two atypical neuroleptics which may represent a new era in the treatment of schizophrenia. The findings from local drug trials and clinical reports are summarised. Both clozapine and risperidone are efficacious in reducing the psychotic symptomatology of schizophrenia as well as inducing less extrapyramidal side-effects. Differences in plasma clozapine levels were found in local Chinese patients when compared to American subjects. Combined use of clozapine and risperidone may give rise to adverse reactions. Both clozapine and risperidone are efficacious and safe in the treatment of schizophrenia.
Antipsychotic Agents↗
Screening for depression among acutely ill geriatric inpatients with a short Geriatric Depression Scale.
BACKGROUND: Depression is not uncommon among acutely ill geriatric inpatients. METHOD: The performances of shorter versions of the Geriatric Depression Scale (GDS) in screening for depression among acutely ill geriatric inpatients were examined. RESULTS: A cut-off of 2/3 gives the best sensitivity (88%) and specificity (75%) for the 10-item version (GDS10). A cut-off of 0/1 gives the best sensitivity (72%) and specificity (90%) for the 4-item version (GDS4). A positive response to item 6 ("Do you often feel helpless?") on the GDS10 gave a sensitivity of 76% and specificity of 75%. Patients found the GDS10 tolerable and acceptable. CONCLUSION: Both shorter versions of the GDS may be utilized in screening for depression among acutely ill geriatric inpatients.
Aged↗
Panic disorder in Singapore: clinical features and comparisons with generalised anxiety disorder.
Fifty-eight outpatients with panic disorder (PD) were examined to determine their clinical features in comparison with a cohort of 52 patients with generalised anxiety disorder (GAD). Both groups were of comparable age, sex, educational level, marital status and ethnicity. PD patients were more likely to complain of palpitations, breathlessness, chest pain, numbness, choking sensations and especially fear of dying. GAD patients tended to complain of feeling tense, insomnia, headaches, weakness, restlessness and muscle aches. PD patients had greater comorbidity especially with agoraphobia and depression. Contrary to other reports, there were more males than females in both groups but alcohol dependence and suicide attempts were relatively rare. PD symptoms seemed more distressing, caused more social and occupational disruption, led to more requests for medical investigations and earlier psychiatric consultations. These factors seemed to suggest that panic disorder is a more severe illness than generalised anxiety disorder.
Adult↗
Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells.
Although the activation domains within early growth response gene protein 1 (Egr-1) have been mapped, little is known of the kinases which phosphorylate Egr-1 and how phosphorylation correlates with the transcriptional activity of Egr-1. In this study we report that casein kinase II (CKII) co-immunoprecipitates with Egr-1 from NIH 3T3 cell lysates. The association of Egr-1 and CKII requires the C terminus of Egr-1 and CKII phosphorylates Egr-1 in vitro. The in vitro phosphorylation of Egr-1 by CKII and that induced by serum in vivo was compared by examining the CNBr-digested fragments of the phosphorylated Egr-1. CKII strongly phosphorylates fragments 7 and 10 which cover part of the activation/nuclear localization and DNA binding domains of Egr-1. CKII also phosphorylates, albeit weakly, fragments 5 and 8 which cover part of activation domain and the entire repression domain of Egr-1, respectively. Strong phosphorylation on fragment 10 as well as fragment 5 was also observed in Egr-1 immunoprecipitated from serum-induced, 32P-labeled cells. CKII phosphorylation of Egr-1 resulted in a decrease of its DNA binding as well as its transcriptional activities.
3T3 Cells↗
Management of insomnia.
Insomnia is a common problem and studies in Singapore and abroad have shown that up to a third of any population studied has experienced insomnia. There is also increasing awareness of insomnia as a health risk. Current views of the problem not only focus on the disturbed sleep pattern but also on the daytime consequences. Younger adults tend to experience sleep latency problems and older adults, sleep maintenance problems. Sleep varies from person to person and according to age. There are no normative values to help in the diagnosis of insomnia but some features typical of insomnia have been noted. The aetiologies of insomnia are diverse and must be determined in the assessment of patients. Treatment of insomnia is non-pharmacologic and/or pharmacologic therapy. There are an increasing number of studies on the various treatments and at present a combination of both types appears best in the long-term management of the problem.
Behavior Therapy↗
Psychiatric day centres--the Singapore experience.
Psychiatric Day Centres are an important aspect of psychiatric community services and care. In Singapore we have developed our Day Centres with the needs of our own patients in mind. At present there are four Psychiatric Day Centres and they focus on vocational and psychosocial rehabilitation. A wide range of structured activities are provided at each of the Day Centres and the programmes are individualised as far as possible to meet the needs of each patient. A multidisciplinary team looks after each patient. This paper outlines the historical aspects of Psychiatric Day Centres and highlights the objectives of the Day Centres administered by Woodbridge Hospital. Patients are grouped into three categories according to their occupational and social skills; programmes and care are provided according to their needs. Of the one hundred and eighty attenders, the sex distribution is almost equal and they are mainly in the twenty to forty-nine age group. Schizophrenia is the most common illness among the attenders and the majority are in the Sheltered Work Group. More than half of them had attended a Day Centre for between one to two years and less than a third had recent admissions to hospital.
Adult↗
Editing of the mitochondrial small subunit rRNA in Physarum polycephalum.
Post-transcriptional insertion, substitution or deletion of nucleotides in RNA (RNA editing) has been observed in RNAs from a number of organisms but always in messenger RNA or transfer RNA. We report here that the 17S rRNA of the mitochondrial ribosome of Physarum polycephalum is edited at 40 sites with single cytidine insertions. The locations of the editing sites are fairly evenly distributed throughout the RNA and do not correspond to any obvious feature of the primary sequence or secondary structure. In addition to these cytidine editing sites are editing sites in which a nucleotide other than cytidine is inserted. At two sites a uridine is inserted and at two sites adenosine residues are inserted. This is the first report of mixed nucleotide insertional editing. These results imply that the editing mechanism in Physarum may be different from those proposed for the kinetoplastid protozoa.
Animals↗
P element mediated germ line transformation of Drosophila melanogaster with the Tc1 transposable DNA element from Caenorhabditis elegans.
Questions relating to the origin and regulation of mobile genetic elements are currently of considerable interest. Since it is now possible to address more precisely issues concerning the entry, dispersion, and regulation of elements within a virgin genome, one approach that may afford a better understanding of transposable elements in general could be provided by interspecific DNA transformation. Therefore, the Tc1 transposable DNA element from Caenorhabditis elegans was chosen as a proposed invading element of the Drosophila melanogaster genome. The basis for this selection resided in the inherent structural and functional similarities, as well as sequence identities, between the Caenorhabditis element and elements innate to Drosophila (e.g., P, HB1, and Uhu). Initial investigations were carried out to define a clone carrying an intact Tc1 element. This Tc1 element was inserted into a P transposon vector and two P-Tc1-ry+ constructs, differing only in insert orientation, were identified. P element mediated germ line transfer was then used to generate a transformant that was genetically and molecularly identified as containing a single, structurally intact Tc1 element at cytological location 64C4-5 on the third chromosome. The single P[(Tc1,ry+)]SAS-B insertion was thereafter mobilized by using a P[ry+ delta 2-3] element as a transposase source, and the genetic and molecular data suggested that the insertion had been successfully reintegrated to a variety of genomic locations. On the basis of genetic and molecular analyses, the Tc1 element in the P[Tc1,ry+)] transformed stock is not highly unstable in germ line and somatic tissues.
Animals↗
A postmarketing surveillance study of zopiclone in insomnia.
Zopiclone, a novel cyclopyrrolone compound has recently become available for the treatment of insomnia in Singapore. Pharmacodynamic and pharmacokinetic studies have shown it to be an effective hypnotic with a good safety profile and minimal side-effects. The efficacy of Zopiclone was studied in a group of patients with insomnia (n = 40). The study group comprised patients with and without a psychiatric diagnosis. About two-thirds (65%) of the patients had been on hypnotics previously without relief of the insomnia. There was improvement in the various sleep parameters studied: sleep latency, sleep duration, night awakening, sleep quality, dreams, "day-after" effects. The drug was well-tolerated and only four patients experienced minor side-effects.
Adult↗
Detection and characterization of cellular EGR-1 binding to its recognition site.
Most of what is known of the Egr-1 DNA binding site GCGGGGGCG was originally identified by experiments using DNA sequences and bacterially expressed or in vitro translated EGR-1 protein. Here we report the binding of cellular EGR-1 protein derived from HeLa, mouse and human fibroblasts to its consensus sequence. Binding is strongly but transiently stimulated in these cells by serum, phorbol ester, or by okadaic acid, an inhibitor of protein serine/threonine phosphatases 1 and 2A, suggesting the regulation of this gene expression and its DNA binding activity to be under the control of protein kinase(s) and phosphatase(s). When EGR-1 synthesis is stimulated under the above conditions, binding of the transcription factor Sp1 to its recognition site in the Egr-1 promoter is reduced with a concomitant appearance of EGR-1 DNA binding. This is likely a result of competition between Sp1 and the newly synthesized EGR-1, since there is a partial overlap in the binding sequences recognized by these proteins. In cotransfection experiments EGR-1 activated transcription through multiple copies of GCGGGGGCG 5' to a minimum promoter of c-fos. Interestingly, EGR-1 is shown to down-regulate the transcription of its own gene expression, whereas Sp1 activated Egr-1 gene expression. The detection of cellular EGR-1 binding to the Egr-1 consensus sequence in the different cell types provides a model for studying the mechanism by which an immediate-early gene is regulated by various ligands.
3T3 Cells↗
Insertional editing in mitochondria of Physarum.
RNA produced from a number of genes on the mitochondrial (mt) DNA of Physarum polycephalum have nucleotides inserted at specific sites in their sequence. These insertions are spaced at approximately 25 nucleotide intervals and create open reading frames in mRNA and functional structure in tRNAs and rRNAs. Although most of the insertions at a site are single cytidines; single uridines and certain dinucleotides containing adenosine and guanosine as well as cytidine and uridine are also occasionally inserted at certain sites. This mixed nucleotide insertional RNA editing is unique among currently characterized editing systems.
Amino Acid Sequence↗
The day release scheme at View Road Hospital.
Psychiatric rehabilitation has been carried out in View Road Hospital since 1975. The training and programmes have been developed over the years and are now individualised according to each patient's abilities, handicaps and needs. The various steps in rehabilitation are outlined. The emphasis in View Road Hospital is on work rehabilitation and social functioning so that the patient can adapt to outside life. Its success is reflected in the Day Release Scheme. Of the 250 patients in View Road Hospital, 92 patients are now on this Day Release Scheme. The majority are young (30-49 age group) and have secondary education. The criteria for this scheme are described.
Activities of Daily Living↗
Psychiatric illness in Filipino maids admitted to Woodbridge Hospital.
This is a retrospective and descriptive study of 44 Filipino maids who had a psychiatric illness in Singapore and were admitted to the state psychiatric hospital. Of those with psychosis, one quarter was diagnosed to have a Brief Reactive Psychosis, 2 had a Depressive illness, whilst 3 had a Schizophrenic illness. One-fifth had symptoms of an Atypical Psychosis. The onset of illness occurred at the sixth week of stay in Singapore, in the majority of the group. Psychosocial and social-cultural factors were considered as causative to the failure of adaptation resulting in a breakdown of coping mechanisms leading to the illness. Educational and marital status, and lack of integration with the new environment are some of the factors discussed. Life events occurring before the onset of illness were mainly financial and relationship difficulties. Two experienced deaths in their families at home. Auditory hallucinations, present in twenty-six of the group, and delusions, present in sixteen, were the main symptomatology discussed. The delusions had mainly sexual and religious themes. Seven had a history of suicidal attempts.
Adult↗
Protein phosphatase inhibitors induce the sustained expression of the Egr-1 gene and the hyperphosphorylation of its gene product.
The immediate-early gene Egr-1 is strongly and rapidly induced in human and mouse Balb/c fibroblasts by okadaic acid and calyculin A, both specific inhibitors of protein serine/threonine phosphatases 1 and 2A. In contrast to the transient induction of the Egr-1 gene by serum or phorbol 12-myristate 13-acetate, these phosphatase inhibitors stimulated a sustained induction of the Egr-1 gene. The induction is shown to occur transcriptionally and is sustained post-transcriptionally. Okadaic acid-induced Egr-1 mRNA is significantly more stable than serum-induced Egr-1 mRNA. The half-life of serum-induced Egr-1 mRNA is estimated to be 12 min, compared with a half life of 2 h for okadaic acid-induced Egr-1 mRNA. Okadaic acid also induced the expression of the related immediate-early genes Egr-2 and Egr-3 albeit to a lesser extent than Egr-1. Treatment of cells with okadaic acid and calyculin A also induced the synthesis of Egr-1 protein. The Egr-1 protein is weakly or not phosphorylated in quiescent cells, but multiple species of the phosphorylated forms of the Egr-1 protein are detected in cells treated with either of the phosphatase inhibitors. Simultaneous treatment of cells with TPA and okadaic acid synergistically induced Egr-1 gene expression, and H7 strongly inhibits this induction. Taken together, the results indicate that the induction of Egr-1 gene transcription and the phosphorylation of the induced Egr-1 protein are under the control of protein kinase(s) and protein phosphatase(s). The phosphorylation and dephosphorylation of Egr-1 protein may play a role in controlling cell growth.
3T3 Cells↗