Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
Add more filters










Publication year range
1.
PLoS One ; 19(3): e0292442, 2024.
Article in English | MEDLINE | ID: mdl-38547110

ABSTRACT

BACKGROUND: Although the benefits of regular physical activity (PA) after stroke are well established, many stroke survivors do not achieve recommended PA levels. To date, studies exploring determinants to PA have not used a behaviour change theory and focused on stroke survivors with physical disabilities. As a precursor to an intervention development study, we aimed to use the Theoretical Domains Framework (TDF) to identify factors influencing PA in stroke survivors with physical disabilities in Singapore. METHODS: Between November 2021 and January 2022, we conducted interviews with 19 community-dwelling stroke survivors with a weak arm and/or leg. An interview guide based on the TDF was developed. We analysed the data deductively by coding interview transcripts into the theoretical domains of the TDF, and then inductively by generating themes and belief statements. To identify relevant TDF domains, we prioritised the domains based on the frequencies of the belief statements, presence of conflicting belief statements and evidence of strong belief statements. RESULTS: Eight of the 14 TDF domains were relevant, and included environmental context and resources, knowledge, social influences, emotion, reinforcement, behavioural regulation, skills and beliefs about capabilities. The lack of access, suitable equipment and skilled help often limited PA participation at public fitness spaces such as parks, gyms and swimming pools (environmental context and resources). While a few stroke survivors expressed that they had the skills to engage in regular PA, most expressed not knowing how much and how hard to work, which exercises to do, which equipment to use and how to adapt exercises and equipment (knowledge and skills). This often left them feeling afraid to try new activities or venture out to new places for fear of the unknown or adverse events (e.g., falls) (emotion). For some, doing the activities in a group encourage them to get out and engage in PA (social influences). CONCLUSIONS: In stroke survivors with physical disabilities, environmental context and resources had a significant influence on PA participation, and this often had a spill over effect into other domains. Our results inform a complex behaviour change intervention to improve PA after stroke, and has implications for intervention design for people with physical disabilities.


Subject(s)
Disabled Persons , Exercise , Humans , Qualitative Research , Emotions , Survivors/psychology
2.
Resuscitation ; 195: 110087, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38097108

ABSTRACT

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.


Subject(s)
Cardiopulmonary Resuscitation , Emergency Responders , Out-of-Hospital Cardiac Arrest , Humans , Smartphone , Cardiopulmonary Resuscitation/methods , Defibrillators , Out-of-Hospital Cardiac Arrest/therapy
3.
Knee ; 27(1): 26-35, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31917106

ABSTRACT

PURPOSE: Osteoarthritis (OA) of the knee is a multifactorial degenerative disease typically defined as the 'wear and tear' of articular joint cartilage. However, recent studies suggest that OA is a disease arising from chronic low-grade inflammation. We conducted a study to investigate the relationship between chronic inflammatory mediators present in both the systemic peripheral blood system and localised inflammation in synovial fluid (SF) of OA and non-OA knees; and subsequently made direct comparative analyses to understand the mechanisms that may underpin the processes involved in OA. METHODS: 20-Plex proteins were quantified using Human Magnetic Luminex® assay (R&D Systems, USA) from plasma and SF of OA (n = 14) and non-OA (n = 14) patients. Ingenuity Pathway Analysis (IPA) software was used to predict the relationship and possible interaction of molecules pertaining to OA. RESULTS: There were significant differences in plasma level for matrix metalloproteinase (MMP)-3, interleukin (IL)-27, IL-8, IL-4, tumour necrosis factor-alpha, MMP-1, IL-15, IL-21, IL-10, and IL-1 beta between the groups, as well as significant differences in SF level for IL-15, IL-8, vascular endothelial growth factor (VEGF), MMP-1, and IL-18. Our predictive OA model demonstrated that toll-like receptor (TLR) 2, macrophage migration inhibitory factor (MIF), TLR4 and IL-1 were the main regulators of IL-1B, IL-4, IL-8, IL-10, IL-15, IL-21, IL-27, MMP-1 and MMP-3 in the plasma system; whilst IL-1B, TLR4, IL-1, and basigin (BSG) were the regulators of IL-4, IL-8, IL-10, IL-15, IL-18, IL-21, IL-27, MMP-1, and MMP-3 in the SF system. CONCLUSION: The elevated plasma IL-8 and SF IL-18 may be associated with the pathogenesis of OA via the activation of MMP-3.


Subject(s)
Cartilage, Articular/metabolism , Interleukin-18/metabolism , Interleukin-8/metabolism , Knee Joint/metabolism , Osteoarthritis, Knee/metabolism , Plasma/metabolism , Synovial Fluid/metabolism , Aged , Biomarkers/metabolism , Cartilage, Articular/pathology , Female , Humans , Knee Joint/pathology , Male , Osteoarthritis, Knee/pathology
4.
Eur J Cancer ; 89: 42-48, 2018 01.
Article in English | MEDLINE | ID: mdl-29227816

ABSTRACT

AIM: To determine the value of mammography and breast ultrasound (US) in predicting outcomes in HER2 positive breast cancer patients (pts) within Neo-ALTTO trial. PATIENTS AND METHODS: Mammography and US were required at baseline, week 6 and surgery. Two independent blinded investigators reviewed the measurements and assigned the corresponding response category. Pts showing complete or partial response according to RECIST (v1.1) were classified as responders. The association between imaging response at week 6 or prior to surgery was evaluated with respect to pathological complete response (pCR) and event-free Survival (EFS). RESULTS: Of the 455 pts enrolled in the trial, 267 (61%) and 340 (77%) had evaluable mammography and US at week 6; 248 (56%) and 309 (70%) pts had evaluable mammography and US prior to surgery. At week 6, 32% and 43% of pts were classified as responders by mammography and US, respectively. pCR rates were twice as high for responders than non-responders (week 6: 46% versus 23% by US, p < 0.0001; 41% versus 24% by mammography, p = 0.007). Positive and negative predictive values of mammography and US prior to surgery were 37% and 35%, and 82% and 70%, respectively. No significant correlation was found between response by mammography and/or US at week 6/surgery and EFS. CONCLUSIONS: Mammography and US were underused in Neo-ALTTO although US had the potential to assess early response whereas mammography to detect residual disease prior to surgery. Our data still emphasise the need for further imaging studies on pts treated with neoadjuvant HER2-targeted therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast/diagnostic imaging , Quinazolines/therapeutic use , Receptor, ErbB-2/analysis , Trastuzumab/therapeutic use , Adult , Aged , Breast Neoplasms/chemistry , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/mortality , Female , Humans , Lapatinib , Mammography , Middle Aged , Neoadjuvant Therapy , Quinazolines/administration & dosage , Trastuzumab/administration & dosage
5.
Malays Orthop J ; 11(2): 1-6, 2017 Jul.
Article in English | MEDLINE | ID: mdl-29021871

ABSTRACT

Despite increasing use of bone graft in Malaysia, there was still lack of data to quantify knowledge level on bone banking among orthopaedic community who are involved in transplantation related work. Therefore, a survey on awareness in tissue banking specifically bone banking, usage and choice of bone grafts was conducted. From 80 respondents, 82.5% were aware about tissue banking however only 12.5% knew of the existence of tissue banks in Malaysia. Femoral head was the bone allograft most often used as a substitute to autograft. Only 34.8% respondents preferred irradiated bone grafts whilst 46.9% preferred nonirradiated, indicating the need to educate the importance of radiation for sterilising tissues. Exhibition was the most preferred medium for awareness programme to disseminate information about bone banking in the orthopaedic community. The professional awareness is necessary to increase the knowledge on the use of bone graft, hence to increase bone transplantation for musculoskeletal surgeries in the country.

6.
Biosens Bioelectron ; 26(8): 3666-9, 2011 Apr 15.
Article in English | MEDLINE | ID: mdl-21367597

ABSTRACT

This paper unveils a platform to develop a compact, simple, reusable and disposable, and cost effective hand-held urinalysis device for home-health-care and doctor's office uses. A polymeric optical waveguide and colorimetric absorption were used as an optical sensor and sensing mode, respectively. The results of the tests show that the device was able to deliver quantitative results with the detection limits better than 0.1g/L, 0.2g/L, 0.025 g/L, and 0.1g/L for glucose, creatinine, albumin and total protein, respectively. There are some superiorities of this device as compared to the dip-stick counterpart, that are, better sensitivity, ability to deliver quantitative results and reusability. The device is being further miniaturized to use a LED and photodiode as a light source and detector, respectively. It is believed the device has potential for early diagnostic and wellness monitoring tool.


Subject(s)
Biosensing Techniques/instrumentation , Polymers/chemistry , Urinalysis/instrumentation , Albuminuria/diagnosis , Blood Glucose/analysis , Calibration , Creatinine/urine , Glycosuria/diagnosis , Humans , Proteinuria/diagnosis
7.
Surg Endosc ; 21(6): 879-84, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17103269

ABSTRACT

BACKGROUND: Thoracoscopic mobilization of the esophagus for pharyngolaryngoesophagectomy allows dissection under direct vision, and therefore it potentially results in fewer complications than conventional transhiatal mobilization. In this article we report our experience with this approach. It was also hypothesized that a learning curve existed and that results have improved over time. PATIENTS AND METHODS: From July 1994 until January 2004, 57 patients underwent pharyngolaryngoesophagectomy in our institution. Intraoperative events and postoperative outcome were prospectively documented, and long-term follow-up data were also studied. Results were compared between the first 30 patients and the last 27 patients. RESULTS: There were no significant differences between the two groups with respect to the various clinicopathological characteristics. There was no difference in the median thoracoscopic time between the first 30 and last 27 patients at 90 and 75 min, respectively, p = 0.18. For the complete procedure there was significantly less blood loss in the later group; median (range) blood loss 700 (164-3000) ml versus 400 (100-1200) ml, p = 0.002. Overall pulmonary complications occurred in 12 patients (40%) in the first group versus 13 (48%) in the second group, p = 0.6. The incidence of atrial arrhythmia was also similar, affecting 6 (20%) patients and 3 (11%), respectively, p = 0.47. Hospital mortality rates were 13.3% and 7.4%, p = 0.67. Two-year survival rates were no different (46% versus 45% p = 0.85). CONCLUSIONS: Although, subjectively, operating skills have improved over time, better results in the second half of this series could not be demonstrated clearly, likely because the operating surgeons had prior extensive experience in esophageal and thoracoscopic procedures.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy , Head and Neck Neoplasms/surgery , Laryngectomy , Pharyngectomy , Thoracoscopy/statistics & numerical data , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Otorhinolaryngologic Neoplasms/surgery , Prospective Studies , Thyroid Neoplasms/surgery
8.
Med J Malaysia ; 61 Suppl A: 97-9, 2006 Feb.
Article in English | MEDLINE | ID: mdl-17042241

ABSTRACT

We report a case of 20-year-old man who presented with bilateral femoral nerve palsy following resuscitation for traumatic massive blood loss and its consequence. A high suspicious index for this complication may lead to its early recognition. Its related pathoanatomy is discussed based on the described evidences in the literature. Nonoperative treatment remains as a recommended option for coagulopathy-related neuropathy.


Subject(s)
Amputation, Traumatic/surgery , Disseminated Intravascular Coagulation/complications , Femoral Nerve/pathology , Femoral Neuropathy/etiology , Adult , Amputation, Traumatic/complications , Blood Coagulation Disorders/complications , Disseminated Intravascular Coagulation/diagnosis , Femoral Neuropathy/diagnosis , Humans , Intraoperative Complications , Male , Paralysis/diagnosis , Paralysis/etiology
9.
Singapore Med J ; 47(1): 71-4, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16397726

ABSTRACT

Melioidosis is caused by an infection by Burkholderia pseudomallei. Osteomyelitis is a recognised manifestation of melioidosis but Burkholderia pseudomallei is a relatively rare aetiological agent in musculoskeletal infections. We report a 32-year-old diabetic man with septicaemia due to melioidotic infection of the spleen, liver and distal femur. The osteomyelitis relapsed despite being treated with the standard radical debridement and insertion of gentamycinimpregnated polymethylmetacrylate (PMMA) beads, followed by an optimal antibiotic therapy. The PMMA-gentamycin beads were then removed. The bone defect was debrided and packed with calcium hydroxyapatite blocks filled with ceftazidime powder. The osteomyelitis was successfully treated and the patient remained free of infection four years postoperatively. Computed tomography demonstrated successful incorporation of the calcium hydroxyapatite into host bone.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Ceftazidime/administration & dosage , Melioidosis/drug therapy , Osteomyelitis/drug therapy , Adult , Burkholderia pseudomallei/isolation & purification , Drug Administration Routes , Durapatite , Femur/microbiology , Follow-Up Studies , Humans , Male , Osteomyelitis/etiology
10.
Int J Radiat Oncol Biol Phys ; 64(2): 374-81, 2006 Feb 01.
Article in English | MEDLINE | ID: mdl-16213105

ABSTRACT

PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.


Subject(s)
Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/pathology , Cisplatin/administration & dosage , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Radiation Injuries/complications , Stomatitis/etiology , Survival Analysis
11.
Med J Malaysia ; 60 Suppl C: 14-6, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16381276

ABSTRACT

A prospective cohort study was undertaken at two centers to look for the incidence of deep vein thrombosis (DVT) following knee arthroscopic surgery. Eighty-four patients who had 90 arthroscopic procedures were reviewed. The relevant risk factors: past or family history of DVT, smoking, oral contraceptives, body weight, haemoglobin level, platelet count, tourniquet time and type of anaesthesia were documented. All patients were subjected to preoperative and post-operative duplex ultrasound. Only one patient (1.2 %) was noted to have DVT involving the peroneal vein. We concluded that the incidence of DVT after knee arthroscopy was very low in this study population.


Subject(s)
Arthroscopy/adverse effects , Knee Joint/surgery , Venous Thrombosis/etiology , Adolescent , Adult , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Venous Thrombosis/epidemiology
12.
Med J Malaysia ; 59 Suppl F: 69-71, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15941169

ABSTRACT

We report a case of delayed diagnosis of tarsal tunnel syndrome caused by a ganglion arising from the talo-calcaneal joint. Unusually the symptoms were mainly due to the lateral planter nerve compression with a positive Tinel's sign. A surgical decompression was successful in relieving the dysaesthesia in spite of a 7 years history.


Subject(s)
Ganglion Cysts/complications , Tarsal Tunnel Syndrome/etiology , Biopsy, Needle , Calcaneus , Decompression, Surgical/methods , Diagnosis, Differential , Female , Ganglion Cysts/diagnosis , Ganglion Cysts/surgery , Humans , Magnetic Resonance Imaging , Middle Aged , Rupture, Spontaneous , Tarsal Tunnel Syndrome/diagnosis , Tarsal Tunnel Syndrome/surgery
13.
Leuk Lymphoma ; 44(10): 1823-5, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14692542

ABSTRACT

A 19-year old girl suffered from relapse of chronic myeloid leukemia (CML) after bone marrow transplantation. The disease was controlled by interferon and imatinib mesylate, but was complicated by autoimmune hyperthyroidism. She presented with unilateral proptosis with no extraocular muscle or visual defect at 26 months follow-up. Systemic investigations showed no recurrence of leukemia or thyrotoxicosis. Magnetic resonance imaging revealed an extensive retro-orbital base of skull lesion. A trans-oral biopsy showed fibrous dysplasia and continuous observation was advised. The unusual sequence of events and the differential diagnoses for unilateral proptosis in post bone marrow transplantation (BMT) cases are discussed.


Subject(s)
Bone Marrow Transplantation , Fibrous Dysplasia of Bone/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Neoplasm Recurrence, Local/diagnosis , Orbital Neoplasms/diagnosis , Adult , Benzamides , Exophthalmos/etiology , Female , Fibrous Dysplasia of Bone/etiology , Humans , Hyperthyroidism/etiology , Imatinib Mesylate , Interferons/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/etiology , Orbital Neoplasms/etiology , Piperazines/therapeutic use , Pyrimidines/therapeutic use
15.
Australas Radiol ; 45(3): 305-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11531753

ABSTRACT

The rib is an uncommon site of osteosarcoma. With the use of adjuvant chemotherapy and aggressive surgical resection of the metastatic pulmonary lesions, extrapulmonary metastases are becoming more clinically evident. Primary rib osteosarcoma with extrapulmonary metastasis is exceedingly rare. A case is reported, showing that the pattern of metastasis of rib osteosarcoma is similar to that of primary bone osteosarcoma. The liver metastasis occurred after resection of the metastatic pulmonary lesions. A CT scan of the primary rib lesion and liver metastasis both showed a lace-like enhancement pattern, its histological appearance corresponding with neoplastic osteoid. With the increasing use of CT abdomen for localization of extrapulmonary metastases, lace-like enhancement may be seen more readily in the future.


Subject(s)
Bone Neoplasms/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Osteosarcoma/diagnostic imaging , Osteosarcoma/secondary , Ribs/diagnostic imaging , Tomography, X-Ray Computed , Adult , Bone Neoplasms/pathology , Female , Humans , Liver Neoplasms/secondary , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Ribs/pathology , Tomography, X-Ray Computed/methods
16.
Histopathology ; 38(6): 510-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11422494

ABSTRACT

AIMS: Hyaline-vascular Castleman's disease (HVCD) and follicular dendritic cell (FDC) sarcoma occurring in the nasopharynx are both extremely rare. We report the first case of transformation of the former into the latter as documented by sequential biopsies. The steps involved in the transformation were described in detail and the possible role of p53 studied. METHODS AND RESULTS: The patient presented at the age of 23 years with nasopharyngeal HVCD. Hyaline- vascular Castleman's disease with FDC overgrowth was diagnosed in a recurrence 8 years later, and a frank FDC sarcoma developed at the same site 11 years after initial presentation. The patient remained disease-free 3 years after excision and adjuvant chemotherapy. The FDC sarcoma comprised swirling fascicles of spindly cells with indistinct cell borders. The tumour cells expressed the FDC markers CD21, CD35 and CNA.42 and in-situ hybridization for Epstein-Barr virus-encoded RNAs was negative. Over-expression of p53 protein was observed in the FDC sarcoma and an increased number of weakly p53-positive spindly cells could also be demonstrated in the HVCD specimen. This finding suggested a possible role of p53 in the evolution from HVCD to FDC sarcoma. Critical analysis of the literature shows that, among the 13 reported cases of FDC sarcoma associated with Castleman's disease, possible progression from the latter to the former is documented in only two cases. CONCLUSIONS: The sequential changes observed in the current case provide further evidence to strengthen the role of HVCD as a possible precursor of FDC sarcoma. There is a possible role of p53 in the transformation process but confirmation by future studies is needed.


Subject(s)
Castleman Disease/pathology , Dendritic Cells/pathology , Nasopharyngeal Neoplasms/pathology , Nasopharynx/pathology , Sarcoma/pathology , Adult , Antigens, Neoplasm/analysis , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/analysis , Biopsy , Castleman Disease/complications , Cell Transformation, Neoplastic , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Dendritic Cells/chemistry , Doxorubicin/administration & dosage , Humans , Immunoenzyme Techniques , Male , Nasopharyngeal Neoplasms/chemistry , Nasopharyngeal Neoplasms/etiology , Nasopharyngeal Neoplasms/therapy , Nasopharynx/surgery , Prednisone/administration & dosage , Sarcoma/chemistry , Sarcoma/etiology , Sarcoma/therapy , Treatment Outcome , Vincristine/administration & dosage
17.
Br J Dermatol ; 143(2): 408-10, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10951154

ABSTRACT

Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL) is a rare cutaneous T-cell lymphoma. The optimal treatment of this disease is undefined. A 36-year-old woman presented with swinging pyrexia, weight loss and disseminated SCPTCL involving her limbs and trunk. Typical histological features of panniculitic infiltration with rimming of fat cells and sparing of the dermis and epidermis were seen. Immunophenotyping confirmed a CD8+ cytotoxic T-cell phenotype. The patient was successfully treated with a combination of fludarabine, mitoxantrone and dexamethasone (FND), and has remained in remission 15 months after cessation of treatment. FND may be an effective regimen for aggressive SCPTCL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, T-Cell, Cutaneous/drug therapy , Panniculitis/drug therapy , Skin Neoplasms/drug therapy , Adult , Dexamethasone/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, T-Cell, Cutaneous/pathology , Mitoxantrone/administration & dosage , Panniculitis/pathology , Skin Neoplasms/pathology , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives
18.
Biochemistry ; 33(25): 7857-68, 1994 Jun 28.
Article in English | MEDLINE | ID: mdl-8011649

ABSTRACT

Lysine 318 in the conserved sequence SXXXGXGKS of bacteriophage T7 gene 4A' protein was mutated to an alanine to understand the effect of this substitution on the helicase and primase activities. The dTTPase activity of 4A'/K318A mutant protein was much lower than that of 4A', and both Km and kcat values were affected. The Km of the mutant protein was 3-5-fold higher, and the kcat was about 100-fold lower, than that of 4A'. The mutation did not affect the ability of 4A'/K318A to assemble into hexamers or bind DNA in the presence of MgdTTP. Interestingly, the mutant protein does not bind DNA in the presence of MgdTMP-PCP. The reduced dTTPase activity, however, decreased the helicase activity of the mutant protein to an undetectable level, whereas its primase activity was only 1.5-2.5-fold lower. When 4A'/K318A mutant protein was mixed with 4A', heterooligomers were formed and the helicase and the DNA-dependent dTTPase activities of 4A' were inhibited, but the DNA-independent activity actually increased. The extent of decrease in activities upon heterooligomer formation depended both on the length of time 4A' and 4A'/K318A proteins were incubated and on the concentration of the mutant protein. In addition, the decrease in the dTTPase activity was observed only when the two proteins were incubated in the absence of MgdTTP and DNA, conditions under which both proteins form unstable hexamers. Even though 4A'/K318A does not bind a 30-mer DNA in the presence of MgdTMP-PCP, heterooligomers were capable of binding DNA with the same stoichiometry as 4A'. Protein-DNA cross-linking experiments with (dT)30 and poly(5-BrdU) showed that DNA interacts with five and perhaps all six subunits of 4A'. Therefore, unless heterooligomer restores the ability of the mutant protein to bind DNA in the presence of MgdTMP-PCP, these results suggest that the DNA can bind 4A' by interacting with a few subunits. However, a fully active hexamer is required for both the helicase and the single-stranded M13 DNA-dependent dTTPase activities.


Subject(s)
Bacteriophage T7/enzymology , DNA Helicases/chemistry , RNA Nucleotidyltransferases/chemistry , Amino Acid Sequence , Bacteriophage M13 , Base Sequence , Cross-Linking Reagents , DNA Helicases/metabolism , DNA Primase , DNA Primers/chemistry , DNA Replication , DNA, Viral/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/metabolism , In Vitro Techniques , Macromolecular Substances , Molecular Sequence Data , Mutagenesis, Site-Directed , Pyrophosphatases/metabolism , RNA Nucleotidyltransferases/metabolism , Structure-Activity Relationship , Virus Replication
SELECTION OF CITATIONS
SEARCH DETAIL
...