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1.
Journal of Chinese Physician ; (12): 1160-1163,1167, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-754285

ABSTRACT

Objective To analyze the distribution of disease types of the epilepsy patients in southern Sichuan,and to provide guidances for the clinical diagnosis and treatment of epilepsy.Methods The complete medical records of inpatients with epilepsy in southern Sichuan who were clearly diagnosed in the Affiliated Hospital of Southwest Medical University from August 2014 to July 2017 were collected and sorted,and classified according to the latest revision of the epilepsy disease standard of the International AntiEpilepsy Alliance in 2017,and the distribution of disease types of these patients were statistically analyzed.Results A total of 454 patients with epilepsy were included in the study,with a male to female ratio of 1.54∶ 1,and the average age is (39.38 ±22.38) years.There were 71 patients under 15 years old,139 cases from 15 years old to 40 years old,189 cases from 41 years old to 65 years old,and 55 cases from over 65 years old.The patients in all ages were mainly classified as generalized onset,and the patients with different origins were mainly motor seizures.The focal onset were most common in the patients with epileptiform spasm from 40 days to 14 years old.The patients of generalized onset were mostly tonic-clonic seizures and under 65 years old.And the patients of unknown onset were mainly concentrated in 15-65 years old and mainly epileptic spasms.Conclusions Most of the patients with epilepsy in southern Sichuan are middle-aged and elderly,and the patients of all ages of different origins are mainly motor seizure,and the distribution of disease types of these patients are different.Moreover,the tonic-clonic seizure and epileptiform spasm are the most common types in these patients.

2.
Kathmandu Univ Med J (KUMJ) ; 14(56): 337-341, 2016.
Article in English | MEDLINE | ID: mdl-29336422

ABSTRACT

Background Hyperactive sympathetic reaction is an important factor for development of hypertension in young individuals. The stress induced increase in blood pressure recovers within very short period of time and those with exaggerated stress induced cardiovascular response at young age have a high risk of blood pressure elevation in future. Objective To determine the cardiovascular reactivity in response to cold and to correlate its relation with factors such as smoking, family history and physical activity. Method Study was conducted in the Department of Pharmacy, Kathmandu University from July to November, 2015. Resting blood pressure was recorded using sphygmomanometer in sitting position after 5 minutes of rest. Out of 130 volunteers, 34 were found to be prehypertensive and equal number of normotensive were recruited randomly to perform the test. The subjects were directed to immerse his/her right hand up to the wrist in cold water of 10˚C for 1 minute. The blood pressure was recorded just before the hand was taken out of the water and then 1.5 minutes and 4 minutes after the withdrawal. Data was analyzed by Student's t test using Microsoft Excel 2007. Result Systolic and diastolic blood pressure increased significantly after cold pressor test in both normal (systolic blood pressure from 110±6.46 to 119±9.45 mmHg and diastolic blood pressure from 71±4.63 to 78±6.15 mmHg) and prehypertensive group (systolic blood pressure from 122±6.75 to 126±8.05 mmHg and diastolic blood pressure from 79±6.78 to 85±7.76 mmHg). Maximum recovery in both systolic and diastolic blood pressure was observed in 2.5 minutes of removal of hand from cold water. Though sharp drop was observed in blood pressure at the end of 2.5 minute in both groups of individuals, the recovery in case of prehypertensive individual was not sharper. In the present study, significant rise in diastolic blood pressure was observed in prehypertensive smoking males. Also the difference was significant (p<0.02) in recovery of diastolic blood pressure between smoker and non smoker prehypertensive group. Conclusion This study suggests that prolonged elevation in blood pressure in response to stress in young individual can be used as marker of development of hypertension in future. Adopting a healthier lifestyle can help to delay the development of hypertension in later life.


Subject(s)
Cold Temperature , Exercise , Hypertension/epidemiology , Hypertension/physiopathology , Medical History Taking , Smoking/epidemiology , Blood Pressure , Female , Humans , Hypertension/diagnosis , Male , Universities , Young Adult
3.
Osteoarthritis Cartilage ; 23(11): 1858-64, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26028139

ABSTRACT

OBJECTIVE: The aim of this study was to examine the osteoarthritis (OA)-related structural changes associated with histological synovitis in end-stage knee OA patients. METHODS: Forty end-stage knee OA patients (female: 88%, mean age: 71.8 y) were enrolled. All participants underwent 3.0-T MRI. The structural changes, such as cartilage morphology, subchondral bone marrow lesion (BML), subchondral bone cyst (SBC), subchondral bone attrition (SBA), osteophytes, meniscal lesion and synovitis, were scored using the whole-organ MRI scoring (WORMS) method. Synovial samples were obtained from five regions of interest (ROIs) of the knee joint during total joint replacement surgery. The associations between the histological synovitis score (HSS) and WORMS or the synovial expression levels of cyclooxygenase (COX)-2, interleukin (IL)-1ß, IL-6 and transforming growth factor (TGF)-ß were examined using Spearman's correlation coefficient. RESULTS: Among the seven OA-related structural changes, the BML, SBC, SBA and synovitis were significantly associated with the HSS (r = 0.33, 0.35, 0.48 and 0.36, respectively), while other morphological changes were not. Although synovial COX-2, IL-1ß or IL-6 expression levels were not associated with the HSS, the synovial TGF-ß expression levels were associated with the HSS. CONCLUSION: The presence of BML, SBC and SBA was associated with histological synovitis in end-stage knee OA patients.


Subject(s)
Bone Cysts/pathology , Bone Marrow Diseases/pathology , Bone Marrow/pathology , Cartilage, Articular/pathology , Magnetic Resonance Imaging/methods , Osteoarthritis, Knee/pathology , Synovitis/pathology , Aged , Bone Cysts/complications , Bone Cysts/metabolism , Bone Marrow Diseases/complications , Bone Marrow Diseases/metabolism , Cross-Sectional Studies , Cytokines/biosynthesis , Female , Humans , Immunohistochemistry , Male , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/metabolism , Synovial Fluid/metabolism , Synovitis/etiology , Synovitis/metabolism
4.
Osteoarthritis Cartilage ; 22(10): 1583-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25278068

ABSTRACT

OBJECTIVE: The aim of the present study was to examine whether the degenerative and morphological changes of articular cartilage in early stage knee osteoarthritis (OA) occurred equally for both femoral- and tibial- or patellar- articular cartilage using magnetic resonance imaging (MRI)-based analyses. DESIGN: This cross-sectional study was approved by the ethics committee of our university. Fifty patients with early stage painful knee OA were enrolled. The patients underwent 3.0 T MRI on the affected knee joint. Healthy volunteers who did not show MRI-based OA changes were also recruited as controls (n = 19). The degenerative changes of the articular cartilage were quantified by a T2 mapping analysis, and any structural changes were conducted using Whole Organ Magnetic Resonance Imaging Score (WORMS) technique. RESULTS: All patients showed MRI-detected OA morphological changes. The T2 values of femoral condyle (FC) (P < 0.0001) and groove (P = 0.0001) in patients with early stage knee OA were significantly increased in comparison to those in the control, while no significant differences in the T2 values of patellar and tibial plateau (TP) were observed between the patients and the control. The WORMS cartilage and osteophyte scores of the femoral articular cartilage were significantly higher than those in the patellar- (P = 0.001 and P = 0.007, respectively) and tibial- (P = 0.0001 and P < 0.0001, respectively) articular cartilage in the patients with early stage knee OA. CONCLUSIONS: The degradation and destruction of the femoral articular cartilage demonstrated a greater degree of deterioration than those of the tibial- and patellar- articular cartilage in patients with early stage knee OA.


Subject(s)
Cartilage Diseases/pathology , Cartilage, Articular/pathology , Femur/pathology , Knee Joint/pathology , Osteoarthritis, Knee/pathology , Patella/pathology , Tibia/pathology , Adult , Aged , Cartilage Diseases/etiology , Case-Control Studies , Cross-Sectional Studies , Disease Progression , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Osteoarthritis, Knee/complications , Osteophyte/etiology , Osteophyte/pathology , Severity of Illness Index
5.
Osteoarthritis Cartilage ; 21(9): 1179-84, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23973128

ABSTRACT

OBJECTIVES: Knee osteoarthritis (OA) pain is suggested to be associated with inflammation and detrimental mechanical loading across the joint. In this cross-sectional study, we simultaneously examined the inflammation and alignment of the lower limb and examined how the pain components varied depending on the disease progression. DESIGN: One-hundred sixty female medial type of early- [n = 74 in Kellgren-Lawrence (K/L) 2] to advanced-stage (n = 96 in K/L >2) knee OA subjects (70.5 years on average) were enrolled. Knee pain was evaluated using a pain visual analog scale (VAS) and the pain-related subcategory of the Japanese Knee Osteoarthritis Measure (JKOM-pain). The serum interleukin (sIL)-6 level reflecting synovitis, and the high sensitivity C-reactive protein (hs-CRP) level were measured to evaluate the severity of inflammation. The anatomical axis angle (AAA) was measured as an alignment index. The ß-coefficient was estimated after adjusting for age and the body mass index (BMI) using a multiple linear regression analysis. RESULTS: Multiple linear regression analyses showed that the sIL-6 levels, but not AAA, associated with the pain VAS [ß = 10.77 (95% confidence interval (CI): 4.14-17.40), P < 0.01] and JKOM-pain scores [ß = 3.19 (95% CI: 1.93-4.44), P < 0.001] in the early stage. Conversely, AAA, but not the sIL-6 levels, was found to be associated with the pain VAS [ß = -1.29 (95% CI: -2.51 to -0.08), P < 0.05] and JKOM-pain scores [ß = -0.49 (95% CI: -0.82 to -0.16), P < 0.01] in the advanced stage. CONCLUSIONS: The presence of a higher level of sIL-6 and the varus alignment of the joint is associated with pain in early- and advanced-stage knee OA patients, respectively.


Subject(s)
Arthralgia/diagnostic imaging , Arthralgia/epidemiology , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/epidemiology , Severity of Illness Index , Aged , Arthralgia/physiopathology , Biomarkers/blood , C-Reactive Protein/metabolism , Cross-Sectional Studies , Disease Progression , Female , Humans , Interleukin-6/blood , Middle Aged , Osteoarthritis, Knee/physiopathology , Pain Measurement , Radiography , Risk Factors , Synovitis/diagnostic imaging , Synovitis/epidemiology , Synovitis/physiopathology , Weight-Bearing/physiology
6.
Nepal Med Coll J ; 13(4): 261-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-23016476

ABSTRACT

This study compared the diagnostic accuracy of Quantitative Buffy Coat (QBC) a fluorescent microscopy test and OptiMAL, an immunochromatographic dip stick test against conventional microscopy for the detection of malaria at a tertiary teaching hospital situated in Eastern Nepal. 100 clinically suspected malaria patients with positive and negative parasitemia were assessed under conventional microscopy. The blood samples withdrawn from these subjects were further evaluated by the QBC Method and OptiMAL dipstick test. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of QBC and OptiMAL tests as compared with microscopy were 100%, 100%, 100%, 100%, 1 and 96%, 100%, 100%, 96.15% and 0.98 respectively. In Nepal, thick and thin blood smears remain the gold standard for malaria species diagnosis in routine diagnostic laboratories. In this study the efficacy of newer malaria rapid diagnostic tests (RDT) surpassed the diagnostic efficacy of clinical microscopy and hence these RDT's will have a greater role in clinical practice. The cost of QBC technique may impose limitations on its use in Nepal but the OptiMAL test is likely to play an important part in urgent malaria diagnosis.


Subject(s)
Chromatography, Affinity/methods , Malaria/diagnosis , Microscopy, Fluorescence , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Nepal , Predictive Value of Tests , Sensitivity and Specificity
7.
Nepal Med Coll J ; 13(4): 272-4, 2011 Dec.
Article in English | MEDLINE | ID: mdl-23016478

ABSTRACT

Intestinal worm infestation is one of the major childhood health problem in Nepal. This study was done to assess the prevalence of intestinal worm infestations among school children aged 6-16 years in a public high school in Kathmandu Nepal. A total of 142 stool samples from healthy students were collected and reported following formol-ether concentration technique. The overall prevalence of intestinal worm infestation was found to be 17.6% (Boys = 22.0% vs girls = 13.5%). Children aged 6-8 years were found to be highly infected with intestinal worms (21.4%) followed by 9-12 years old (18.6%). Those between 13-16 years of age were significantly less infected (10.7%) compared to others (p < 0.05). Ova/cysts of intestinal parasites detected include Trichuris trichiura (32.0%), Ascaris lumbricoides (20.0%), Hymenolepis nana (16.0%), hookworm (8.0%) and 24.0% cases showed mixed parasitic infections.


Subject(s)
Helminthiasis/epidemiology , Intestinal Diseases, Parasitic/epidemiology , Adolescent , Animals , Child , Female , Humans , Male , Nepal/epidemiology , Prevalence
8.
Leukemia ; 16(11): 2302-8, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12399976

ABSTRACT

Infant acute lymphoblastic leukemia (ALL) is characterized by the presence of the proB phenotype (CD10(-)/CD19(+)), poor prognosis and frequent rearrangement of the mixed lineage leukemia (MLL) gene. The most frequent rearrangement is t(4;11)(q21;q23), the role of whose product, the MLL-AF4 fusion transcript, has been extensively studied in leukemogenesis. In a cell line of infant leukemia with MLL rearrangement denoted KP-L-RY, panhandle PCR amplification of cDNA revealed the presence of a fusion transcript, MLL-AF5q31, indicating that AF5q31 is also a partner gene of MLL. In this fusion transcript the MLL exon 6 is fused in frame to the 5' side of the putative transactivation domain of AF5q31. The AF5q31 protein is a member of the AF4/LAF4/FMR2-related family of proteins, which have been suggested to play a role in hematopoietic cell growth and differentiation. The MLL-AF5q31 fusion transcript, although probably rare, appears to be associated with the pathogenesis of infant ALL like MLL-AF4. Co-expression of HoxA9 and Meis1 genes in the KP-L-RY cell line indicated possible functional similarity between MLL-AF4 and MLL-AF5q31. Further understanding of the function of AF5q31 as well as the specific leukemogenic mechanism of MLL-AF5q31 awaits future studies.


Subject(s)
Biomarkers, Tumor/genetics , Neoplasm Proteins/genetics , Oncogene Proteins, Fusion/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Acute Disease , Artificial Gene Fusion , Blotting, Southern , Cell Line , Chromosome Mapping , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 4/genetics , DNA Primers/chemistry , DNA, Neoplasm/analysis , Exons , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Myeloid Ecotropic Viral Integration Site 1 Protein , Myeloid-Lymphoid Leukemia Protein , Neoplasm Proteins/metabolism , Polymerase Chain Reaction , Translocation, Genetic
9.
Oncol Rep ; 8(6): 1255-7, 2001.
Article in English | MEDLINE | ID: mdl-11605044

ABSTRACT

We present a case of a premenopausal woman treated with GnRH agonist for a presumed uterine leiomyoma. This tumor reduced at first, but subsequent surgical specimens revealed a leiomyosarcoma. Magnetic resonance imaging (MRI), one of the most useful modalities for distinguishing between uterine leiomyoma and leiomyosarcoma, was undertaken twice, before GnRH agonist administration and then after 6 months of GnRH agonist administration. Apparent differences were observed between these MRI findings. Tumor-size reduction with GnRH agonist treatment does not always mean that the possibility of a leiomyosarcoma should be ruled out.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Buserelin/therapeutic use , Leiomyoma/diagnosis , Leiomyoma/drug therapy , Leiomyosarcoma/diagnosis , Leiomyosarcoma/drug therapy , Uterine Neoplasms/diagnosis , Uterine Neoplasms/drug therapy , Biopsy, Needle , Female , Humans , Leiomyoma/pathology , Leiomyosarcoma/pathology , Magnetic Resonance Imaging , Middle Aged , Premenopause , Uterine Neoplasms/pathology
10.
Lancet ; 357(9255): 529-30, 2001 Feb 17.
Article in English | MEDLINE | ID: mdl-11229676

ABSTRACT

We developed a novel chromosome banding technique-spectral colour banding (SCAN). With this technique we displayed a multicolour banding pattern that almost entirely correlated with the corresponding G-banding pattern. With SCAN analysis we could identify the chromosome-band origin of double minute chromosomes in gastric cancer. Our preliminary use of this technique suggests that it has significant clinical applications for cytogenetic analysis.


Subject(s)
Chromosome Banding/methods , Carcinoma, Signet Ring Cell/genetics , Chromosomes, Human, Pair 10 , Color , Fluorescence , Humans , Male , Middle Aged , Nucleic Acid Hybridization , Stomach Neoplasms/genetics
13.
J Pharm Sci ; 88(8): 759-62, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10430538

ABSTRACT

The UV absorbance and bitter taste of oxyphenonium bromide (OB), an antiacetylcholine drug, in cyclodextrin (CD) solutions are measured, and the local environment of the binding site and the reduction of the bitter taste intensity are quantitatively estimated from the UV data. The UV spectrum of OB is changed with the addition of alpha-, beta-, and gamma-CD, because the phenyl group of OB is included into the CD cavity. The maximum wavelength, lambda(max), senses environmental changes of OB best among several spectral characteristics. From comparison of lambda(max) between a CD solution and the reference ethanol-water and dioxane-water systems, the dielectric constant of the binding site is evaluated. This value leads us to estimate the microenvironment and structure of the binding site. The suppression of the bitter taste of 4 mM OB by CDs is in the increasing order alpha-CD < gamma-CD < beta-CD. The extent of this suppression can be quantitatively predicted from the UV absorbance by assuming that the free OB molecule alone exhibits the bitter taste, regardless of the kind and concentration of CD. Some implications and limitations of the present approach are discussed.


Subject(s)
Muscarinic Antagonists/analysis , Muscarinic Antagonists/pharmacology , Oxyphenonium/analysis , Oxyphenonium/pharmacology , Taste/drug effects , Cyclodextrins , Environment , Humans , Microchemistry , Muscarinic Antagonists/administration & dosage , Oxyphenonium/administration & dosage , Pharmaceutical Solutions , Spectrophotometry, Ultraviolet
14.
Int J Hematol ; 69(2): 101-4, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10071459

ABSTRACT

We describe two separate episodes of hemophagocytic syndrome (HPS) at an interval of two years in a seemingly immunocompetent male. This case suggests the possible existence of an inherent predisposition to HPS, in which otherwise negligible self-limited viral infection may trigger HPS. Laboratory data for a 16-year-old boy admitted with persistent high grade fever and severe thrombocytopenia disclosed coagulation abnormality, liver damage, and hypercytokinemia. A bone marrow aspiration revealed a proliferation of histiocytes with fresh hemophagocytosis. We diagnosed that he was suffering from HPS. Responding to steroid pulse therapy, he recovered completely and was discharged. After two years of healthy life, he became febrile again and was readmitted. The fever was refractory to antibiotics and was associated with a sudden drop in platelet count. Laboratory data and the bone marrow picture were consistent with those of HPS. He was again successfully treated with steroid. After the second episode, he has been healthy for more than two years.


Subject(s)
Histiocytosis, Non-Langerhans-Cell , Adolescent , Disease Susceptibility , Fever/etiology , Histiocytosis, Non-Langerhans-Cell/diagnosis , Histiocytosis, Non-Langerhans-Cell/immunology , Humans , Immunocompetence , Male , Recurrence , Thrombocytopenia/etiology
15.
Anal Chem ; 71(9): 1733-6, 1999 May 01.
Article in English | MEDLINE | ID: mdl-21662814

ABSTRACT

The bitter taste of oxyphenonium bromide, an antiacetylcholine drug, is suppressed by cyclodextrins. The extent of the suppression can be predicted from the electromotive force measurements with an oxyphenonium bromide-selective electrode. The relationship between the bitter taste intensity and the electromotive force holds true, regardless of the kind and concentration of natural and modified cyclodextrins. This result is explicable on the basis of the observation that both the bitter taste and the electric potential are determined by the concentration of free oxyphenonium bromide. Some implications and limitations of the present approach are discussed.

16.
Cancer ; 82(10): 1963-72, 1998 May 15.
Article in English | MEDLINE | ID: mdl-9587131

ABSTRACT

BACKGROUND: The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma. METHODS: Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens. RESULTS: Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection. CONCLUSIONS: In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS.


Subject(s)
Herpesvirus 4, Human/isolation & purification , Histiocytosis, Non-Langerhans-Cell/virology , Lymphoma, B-Cell/virology , Aged , Aged, 80 and over , Antigens, Viral/analysis , Clinical Laboratory Techniques , Cytokines/blood , Female , Histiocytosis, Non-Langerhans-Cell/complications , Humans , In Situ Hybridization , Lymphoma, B-Cell/complications , Male , Medical History Taking , Middle Aged , Polymerase Chain Reaction , RNA, Viral/analysis , Receptors, Interleukin-2/analysis , Viral Matrix Proteins/analysis
17.
Am J Hematol ; 57(4): 320-5, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9544977

ABSTRACT

Although a breakpoint in the minor breakpoint cluster region (m-bcr) of the BCR gene is observed in about two-thirds of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, this type of genomic rearrangement occurs very rarely in chronic myeloid leukemia (CML). We describe here the eighth case of m-bcr CML, and delineate unique clinical characteristics found in common to the 7 cases reported previously. Monocytosis with a low neutrophil/monocyte ratio resembling chronic myelomonocytic leukemia was the most striking feature of m-bcr CML. Splenomegaly and basophilia were not conspicuous in chronic phase. A high percentage of immature granulocytes and low neutrophil alkaline phosphatase score were the findings in common with classical CML. Lymphoid and myeloid blast changes have been observed at and shortly after presentation so far. We found a hybrid type of blast crisis in the course of m-bcr CML.Thus, m-bcr CML may be a definite subtype of CML, exhibiting distinct clinical characteristics. The presence of fusion product of m-bcr mRNA in an earlier myeloid cell may involve monocytic lineage in addition to myeloproliferative defects.


Subject(s)
Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein-Tyrosine Kinases , Proto-Oncogene Proteins/genetics , Blast Crisis , Chromosome Mapping , Humans , In Situ Hybridization, Fluorescence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/physiopathology , Leukocyte Count , Male , Middle Aged , Proto-Oncogene Proteins c-bcr , Translocation, Genetic/genetics
18.
Biochem J ; 308 ( Pt 1): 297-304, 1995 May 15.
Article in English | MEDLINE | ID: mdl-7755577

ABSTRACT

Chemical modification and inactivation of bovine pancreatic, porcine pancreatic, Naja naja atra and Pseudechis australis phospholipases A2 (PLA2s), belonging to Group I, and of Trimeresurus flavoviridis, Vipera russelli russelli and Agkistrodon halys blomhoffii PLA2s, belonging to Group II, were investigated by the use of a manoalide (MLD)-analogue, 1-(2,5-dihydro-hydroxy-5-oxo-3-furanyl)-8,12-dimethyl-4-formyl-3,7, 11-tridecatrienol. At appropriate time intervals, residual PLA2 activities towards monodispersed, anionic mixed micellar and non-ionic mixed micellar substrates were measured. We tested the protective effect of micellar n-dodecylphosphocholine (n-C12PC) on enzyme inactivation. Inactivation of pancreatic PLA2s (Group I) was only observed towards anionic mixed micellar substrates. This inactivation was completely prevented by the presence of micellar n-C12PC. From a fragmentation study of modified bovine pancreatic PLA2 using lysyl endopeptidase, we speculated that Lys-56 of this enzyme was modified by MLD-analogue and that this modification was responsible for enzyme inactivation. Inactivation of non-pancreatic PLA2s was observed towards all types of substrate, except that no significant inactivation of N. naja atra PLA2 (Group I) towards monodispersed substrate was noted. Micellar n-C12PC protected N. naja atra PLA2 (Group I) completely from inactivation by MLD-analogue, but had lesser protective effects on P. australis PLA2 (Group I), T. flavoviridis and V. russelli russelli PLA2s (Group II). However, no significant protection of A. halys blomhoffii PLA2s (Group II) activity was observed. These results indicate that the inactivation of pancreatic and N. naja atra PLA2s originates from the modification of Lys residues at the interfacial recognition site, and that inactivation of P. australis, T. flavoviridis and V. russelli PLA2s arises from the modification of Lys residues at the catalytic site, interfacial recognition site and regions outside both sites. The inactivation of A. halys blomhoffii PLA2 was assumed to be due to the modification of Lys residues outside the two sites described above.


Subject(s)
Phospholipases A/chemistry , Amino Acid Sequence , Animals , Cattle , Lysine/chemistry , Molecular Sequence Data , Pancreas/enzymology , Phospholipases A/antagonists & inhibitors , Phospholipases A/classification , Phospholipases A2 , Sequence Alignment , Sequence Homology, Amino Acid , Snake Venoms/chemistry , Terpenes
19.
J Biochem ; 116(4): 870-6, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7883763

ABSTRACT

Effects of Ca2+ on the kinetic parameters for the hydrolysis of monodispersed 1,2-dihexanoyl-sn-glycero-3-phosphorylcholine (diC6PC), catalyzed by Group I phospholipases A2 (PLA2s) from Pseudechis australis, Naja naja atra, and bovine pancreas and by Group II enzymes from Vipera russelli russelli, Agkistrodon halys blomhoffii, and Trimeresurus flavoviridis, were studied by the pH-stat assay method at 25 degrees C, pH 7.5-8.2, and an ionic strength of 0.1 or 0.2 in the absence or presence of an amide-type substrate analog, 2-dodecanoyl-amino-1-hexanol-phosphoglycol. The binding of genuine substrate to the Group II enzymes and that of its analog to the Groups I and II enzymes were markedly facilitated by the binding of Ca2+ to the enzymes. On the other hand, the binding of genuine substrate to the Group I enzymes was found to be independent of the Ca2+ binding. The former result suggests that the structures of the Group II enzyme-genuine substrate complexes and both types of enzyme-analog complexes are generally stabilized by the Ca2+ binding, whereas the latter indicates that the structures of the Group I enzyme-genuine substrate complexes are already similar to those of their Ca2+ complexes and that, therefore, these enzyme-substrate interactions are independent of the Ca2+ binding.


Subject(s)
Calcium/pharmacology , Isoenzymes/metabolism , Phosphatidylcholines/metabolism , Phospholipases A/metabolism , Amides/metabolism , Animals , Cattle , Elapid Venoms/enzymology , Hydrolysis , Isoenzymes/antagonists & inhibitors , Kinetics , Phospholipases A/antagonists & inhibitors , Phospholipases A2 , Viper Venoms/enzymology
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