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Biomedical subjects

P Wasi

Publications and source records attributed to P Wasi.

At least 19 recordsLinked to original sources
PubMed1997

Failure of pulse high-dose dexamethasone in chronic idiopathic immune thrombocytopenia.

Idiopathic thrombocytopenic purpura (ITP) is a disorder characterized by increased platelet destruction in the setting of normal megakaryopoiesis. Approximately 20% of patients with ITP are refractory to corticosteroids and splenectomy. Recently, pulse high-dose dexamethasone was reported to be effective in the treatment of chronic ITP in adult patients. We treated 9 patients with severe chronic ITP with monthly high-dose dexamethasone. None of the 9 patients responded with a sustained increase in platelet count. Five of these patients were unable to tolerate the regimen. The failure of high-dose dexamethasone in our hands contrasts with the good results of an earlier publication and suggests that there could be a subset of responders who will require better identification.

Administration, Oral↗
PubMed1997

Presence of immunoglobulins, C3 and cytolytic C5b-9 complement components on the surface of erythrocytes from patients with beta-thalassaemia/HbE disease.

The occurrence of IgG, IgM, IgA, C3 and C5b-9 complement complexes on erythrocytes from 43 patients with beta-thalassaemia HbE disease was investigated. Indirect immunoradiometric assays using radioiodinated protein A were employed to quantify the individual components. We confirmed that circulating erythrocytes from thalassaemic patients contained elevated amounts of IgG, and small but significant amounts of C3. In addition, small but significant amounts of C5b-9 were detected. Levels of cell-bound IgG, C3 and C5b-9 were higher in splenectomized versus non-splenectomized patients. The presence of C5b-9 on circulating cells from five splenectomized patients was confirmed by an ELISA employing a monoclonal antibody specific for a C5b-9 neoantigen. When C5b-9 positive cells from two patients were solubilized with detergent and subjected to sucrose density gradient centrifugation, the terminal complexes sedimented as 25-40S macromolecules, thus behaving as membrane C5b-9 complexes. The presence of C8 and C9 in these high molecular weight fractions was directly demonstrated by Western blotting. These results constitute the first demonstration that circulating diseased erythrocytes may carry low numbers of potentially cytolytic C5b-9 complement complexes which may be partly responsible for the known ionic disturbances found in thalassaemic cells. Both bound C3 and C5b-9 could promote removal of diseased cells in the reticuloendothelial system.

Adult↗
PubMed1997

Human genomics: implications for health.

Human genome research which tries to map and sequence all the 3 billion nucleotides in the entire DNA is progressing rapidly. Completion of the human genome sequencing is expected before the year 2005. Human genes, totalling 50,000-100,000, will be identified, allowing the complete set of proteins--'the proteome' to be known. This together with genomic research in other species will lead to complete understanding of life at the molecular level and also its evolutionary history of 3,500 million years. Genomics will bring about a revolution in biology and health, because it is equivalent to having a 'Biological Periodic Table' which is a foundation for understanding life, health, disease and for deriving of new tools for diagnosis, treatment, prognosis and prevention. Human genomics will give rise to Predictive--Preventive Medicine and Precision Medicine. It will have profound social implications. Preparation for the future is needed for societies to cope with and make proper use of the tremendous changes to be brought about by genomics.

Asia, Southeastern↗
PubMed1995

Severity of beta-thalassemia due to genotypes involving the IVS-I-6 (T-->C) mutation.

Among individuals of Mediterranean or Middle Eastern descent, the IVS-I-6 (T-->C) mutation is one of the most common causes of beta-thalassemia. In this report, we describe the clinical phenotypes of a group of beta-thalassemia patients who are compound heterozygotes for the relatively mild IVS-I-6 (T-->C) beta-thalassemia mutation and more severe beta(+)- or beta (0)-thalassemia mutations. Although most of these patients are transfusion-dependent, the requirement for regular transfusions generally occurred late in childhood. A correlation between concomitant alpha-thalassemia and a mild transfusion-independent phenotype is not apparent, indicating the involvement of other ameliorating determinants.

Adult↗
PubMed1995

Bacterial infection-associated improvement of platelet counts in two patients with chronic and unresponsive idiopathic thrombocytopenic purpura with normal platelet survival studies.

Approximately 20% of adult patients with idiopathic thrombocytopenic purpura (ITP) do not respond to splenectomy and require alternative therapies to achieve a clinically safe platelet count. A small percentage of these patients have very refractory disease and are either unresponsive or poorly responsive to almost any therapy. In this report we describe two patients with chronic and unresponsive ITP with normal platelet survivals. Neither patient had responded to a large variety of treatments including corticosteroids, splenectomy, IVIgG, anti-D, chemotherapy, and ascorbic acid. However, both had a rapid, but short-lived, rise in their platelet count following a bacterial infection. One patient had a rise in platelet count for 6 months following the acute episode of bacteraemia. The second patient had a shorter response of 1 week. It is possible that these two patients represent a subset of patients with ITP who may benefit from cytokine therapy.

Aged↗
PubMed1993

Activation of monocytes for the immune clearance of red cells in beta zero-thalassaemia/HbE.

We have recently provided evidence that IgG antibodies play a role in the destruction of red cells in thalassaemia syndromes. In order further to delineate factors involved in the clearance of thalassaemic cells, monocytes of 30 Thai patients with beta zero-thal/HbE (17 non-splenectomized and 13 splenectomized) and 16 normal controls were examined for their ability to bind and phagocytose normal red cells coated with IgG anti-Rh(D). In beta zero-thal/HbE, the mean number of red cells attached to the monocytes was approximately 3-fold greater than in normal controls and the number ingested 30% higher. Among the non-splenectomized patients, the number of red cells attached to and ingested by the monocytes, correlated inversely with mean basal Hb levels, suggesting that activation of mononuclear phagocytes for the immune clearance of red cells is a factor in determining the severity of the anaemia. As Fc-gamma-RI is of primary importance in the recognition of IgG-coated red cells by monocytes, leucocytes from 10 beta zero-thal/HbE patients (four non-splenectomized and six splenectomized) and five normal controls were investigated for their expression of Fc-gamma-RI by flow cytometry. In beta zero-thal/HbE there was an approximately 3-fold increase in the percentage of leucocytes expressing this receptor; the receptor was up-regulated on monocytes and induced on granulocytes. The up-regulation of Fc-gamma-RI in beta zero-thal/HbE is likely to be an important component in the activation of monocytes and in mediating their enhanced effector function towards antibody-coated cells.

Erythrocytes↗
PubMed1993

Severity differences in beta-thalassaemia/haemoglobin E syndromes: implication of genetic factors.

Genetic factors determining the difference in severity of anaemia in beta-thalassaemia/HbE disease were studied in 90 patients who had haemoglobin levels, at steady state, ranging from 4.2 to 12.6 g/dl. Co-inheritance of alpha-thalassaemia 2 and haemoglobin Constant Spring could significantly decrease the severity of the disease. Inheritance of a beta-thalassaemia chromosome with Xmn I cleavage site at position -158 of the G gamma-globin gene which was linked to the haplotype -+-++ or ++-++, was associated with a milder anaemia. Two copies of these alleles were necessary to produce a significant clinical effect. Increased expression of the G gamma-globin gene and higher production of haemoglobin F, which could reduce the overall globin chain imbalance, were also associated with homozygosity for the Xmn I cleavage site and thus with less severe anaemia. However, this effect was not seen in Xmn I site heterozygotes. Whether the effects of the Xmn I polymorphism, HbF concentration and G gamma/A gamma ratio act separately or through common mechanisms in reducing anaemia remains to be ascertained.

Adolescent↗
PubMed1992

Identification of five rare mutations including a novel frameshift mutation causing beta zero-thalassemia in Thai patients with beta zero-thalassemia/hemoglobin E disease.

6 out of 14 uncharacterized beta-thalassemia alleles from 187 Thai beta-thalassemia/HbE patients were identified by direct sequencing of DNA amplified by polymerase chain reaction. A novel mutation occurring from an insertion of adenosine in codon 95, which results in a shift of the reading frame with terminator at the new codon 101, was detected in one patient. In addition, two frameshift mutations not previously reported among the Thai population were also detected in 3 patients: one with a deletion of thymidine in codon 15 and two with an insertion of cytidine in codons 27/28. A frameshift mutation that occurred from a cytidine deletion in codon 41 was also found in one patient in this study. The remaining case was an amber mutation, GAG-TAG, in codon 43 in exon 2 of the beta-globin gene. These mutations bring the number of mutations known to be present in the Thai population to a total of 20, 15 of which were detected in beta-thalassemia/HbE patients.

Adult↗
PubMed1992

Hypoxemia in thalassemia.

Data are reviewed describing hypoxemia, a newly identified feature in thalassemia. Evidence indicates platelet aggregation in the pulmonary circulation as being a key factor leading to hypoxemia and cor-pulmonale with right heart failure.

Aspirin↗
PubMed1992

Pathogenesis of hypoxemia.

Thrombocytosis and morphological changes in shape and size of circulating platelets are commonly found in splenectomized thalassemia patients. Functional abnormalities of the platelets are evidently related to their fragile nature. Spontaneous aggregation of platelets can easily occur following application of mild pressure either from a stirring magnetic bar or due to centrifugal force. Platelets are hyper-reactive to chemical stimulation and the release of platelet granule contents (eg ATP) together with other membranous lipid metabolites, thromboxane A2 and malondialdehyde is markedly enhanced. The lipid soluble antioxidant, vitamin E is depleted from various blood compartments. The findings suggest that circulating platelets in splenectomized thalassemia are continuously attacked by yet to be identified blood borne factor(s) and the defective platelets could play a pivotal role in the pathogenesis of hypoxemia.

Case-Control Studies↗
PubMed1992

The molecular basis of alpha-thalassemia in Thailand.

Alpha thalassemia is the most common single gene mutation worldwide. In Thailand there exists 15-30% alpha-thalassemia carriers distributed throughout the country. DNA analysis by Southern blot hybridization reveals that the two major alpha-thalassemia alleles, alpha-thalassemia 1 and alpha-thalassemia 2 have different extents of alpha-globin gene deletion. In alpha-thalassemia 1, approximately 20 kb of DNA including the two linked alpha 1-and alpha 2-genes are removed and only the alpha-globin gene is intact. Total deletion of the alpha-globin gene cluster is rarely observed. In contrast, only one alpha-globin gene is deleted in alpha-thalassemia 2 of which two types have been detected, one involving a deletion of 4.2 kb of DNA (leftward type, -alpha 4.2) and another of 3.7 kb (rightward type, -alpha 3.7); the latter being more common than the former in Thailand. Compound heterozygosity for alpha-thalassemia 1 and alpha-thalassemia 2 results in HbH disease while homozygosity for alpha-thalassemia 1 leads to Hb Bart's hydrops fetalis, the most severe form of thalassemic disease. Three alpha-thalassemic hemoglobinopathies have been detected in Thailand, two of which produce a remarkable reduction in gene product. Upon interacting with alpha-thalassemia 1 gene they can lead to HbH disease. The most common in this group is Hb Constant Spring which arises from mutation of the termination codon in the alpha 2-gene resulting in an elongation of the alpha-globin chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Protein Electrophoresis↗
PubMed1991

Hemoglobin constant spring in Bangkok: molecular screening by selective enzymatic amplification of the alpha 2-globin gene.

Hemoglobin Constant Spring (Hb CS) is a hemoglobin variant with an elongated alpha-globin chain secondary to a chain termination mutation. The diagnosis of HbCS by electrophoresis is difficult because it is present in very low amounts in the red cells of heterozygotes. Selective enzymatic amplification of the alpha 2-globin gene and allele-specific hybridization for Hb CS gene provided accurate diagnosis of Hb Constant Spring. We have used this approach to detect the alpha cs mutation in the cord blood that contained all four alpha-globin genes but had Hb Bart on electrophoresis. The alpha cs mutation was found in six subjects whose Hb Bart levels were 3.0, 3.2, 3.7, 4.0, 4.9, and 9.8%. The latter also had -alpha mutation on the other chromosome, giving rise to the genotype alpha cs alpha/-alpha, which produced high Hb Bart. The gene frequency for alpha cs in the Thai calculated from a total of 406 cord blood studied in Bangkok was found to be approximately 0.008.

Base Sequence↗
PubMed1991

Erythroblast- and erythrocyte-bound antibodies in alpha and beta thalassaemia syndromes.

Thirty-five Thai patients with various alpha-thalassaemia (alpha-thal 1/alpha-thal 2, alpha-thal 1/HbCS, HbCS/HbCS) and beta-thalassaemia (beta-thal/HbE, severe and mild form, HbE/HbE) syndromes were examined for the presence of immunoglobulins and C3d on o-tolidine positive erythroblasts in the bone marrow, and for the amounts of IgG of some specificities bound to circulating erythrocytes. In mild, but not in severe beta-thal/HbE and in alpha-thalassaemia, the percentages of Ig-positive erythroblasts were significantly higher than in controls and correlated well with the percentage of IgG-positive erythroblasts. By contrast, the percentages of IgM and C3d positive erythroblasts were low and similar in thalassaemic and control marrows. A substantial proportion of thalassaemic patients showed more erythrocyte-bound IgG than controls, but statistically significant elevations were seen only in severe beta-thal/HbE. Within a particular syndrome erythrocyte-bound IgG was more abundant in splenectomized than non-splenectomized subjects. It showed specificity for spectrin in some beta-thalassaemic patients and for band 3 protein in several individuals with alpha- or beta-thalassaemia. The results suggest that IgG antibodies play a role in the haemolysis of thalassaemia and that they are likely to be involved in the ineffective erythropoiesis in at least some of the syndromes studied.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1990

Hemoglobin Dhonburi alpha 2 beta 2 126 (H4) Val----Gly: a new unstable beta variant producing a beta-thalassemia intermedia phenotype in association with beta zero-thalassemia.

While investigating the mechanism of a beta-thalassemia intermedia phenotype in a 34 year old Thai male, a new Hb variant beta 126 Val----Gly named Hb Dhonburi was discovered. Genetic and structural studies revealed the existence of a beta zero-thalassemia genotype in association with the beta variant. The new variant is unstable but exhibits normal oxygen binding properties. Hb Dhonburi was also discovered in the mother of the propositus in association with Hb E.

1-Propanol↗
PubMed1990

Thai G gamma (A gamma delta beta)zero-thalassemia and its interaction with a single gamma-globin gene on a chromosome carrying beta zero-thalassemia.

Clinical manifestations and hematologic data of thalassemia intermedia were observed in three siblings of a Thai family. Analyses of the hemoglobin of their parents and other siblings indicated that they inherited a delta beta-thalassemia gene from the father and a beta zero thalassemia gene from the mother. Globin gene mapping confirmed that they carry two abnormal beta-globin gene complexes. On one chromosome more than 70 kb of DNA was removed which resulted in G gamma (A gamma delta beta)zero-thalassemia. The deletion started at the Hind III site located just 3' to the G gamma gene, and extended downstream to a region recognized by the p3'N 2.8R probe which is located more than 45 kb from the 3' end of the beta gene. The other chromosome carried a beta zero thalassemia gene, and a 5 kb deletion between the G gamma and A gamma genes which produced a hybrid -GA gamma- gene. A synthetic oligonucleotide probe showed that this beta zero thalassemia arose from a C----T mutation at position 654 of IVS-II in the beta-globin gene.

Adolescent↗
PubMed1990

The molecular basis of beta-thalassemia in Thailand: application to prenatal diagnosis.

To enable the prenatal diagnosis of beta-thalassemia by direct detection of the mutant beta-globin genes, we have determined the spectrum of mutations causing this disease in Thailand. The techniques employed included a combination of synthetic oligonucleotide probe hybridization, direct sequencing of genomic DNA enzymatically amplified by the polymerase chain reaction, and cloning and sequencing of the beta-globin genes. A total of 116 beta-thalassemia genes from 78 Hb E/beta-thalassemia patients and from 19 homozygous beta-thalassemia patients were analyzed, and the mutation was characterized in 112/116 (97%) of them. Eleven mutations were found, of which four (-CTTT in codon 41/42, AAG----TAG in codon 17, C----T in position 654 of the IVS-2 region, and A----G in position -28 upstream of the beta-globin gene) accounted for 83%; two previously undescribed mutations have been identified. The spectrum of beta-thalassemia mutations is similar to that reported among the Chinese. However, within the Thai population itself, patients with homozygous beta-thalassemia show a wider spread of mutations in comparison with the Hb E/beta-thalassemia group, in whom the frameshift 41/42 mutation predominates at a frequency of 62%. This difference in distribution may reflect the difference in ethnic origin of the two groups. Characterization of these mutations should aid the planning of a prenatal diagnosis program for beta-thalassemia in Thailand.

Base Sequence↗