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Biomedical subjects

E George

Publications and source records attributed to E George.

At least 73 records · Page 4Linked to original sources
PubMed1994

Beta-thalassaemia mutations in west Malaysia: a new thalassaemia clinical score system.

The clinical severity of the mutations causing beta-thalassaemia in West Malaysia is presented. Thalassaemia clinical scores (Thal CS), a scoring system, has been formulated to predict clinical severity. It is the type of beta-thalassaemia mutation present that decides on the clinical phenotype. The most severe beta-thalassaemia mutation is assigned a score of 4. A score of 8 indicates a severe thalassaemia phenotype. Alpha-thalassaemia, increased synthesis of Hb F, and glucose-6-phosphate deficiency may ameliorate the clinical condition at phenotype level, and the co-inheritance of hereditary ovalocytosis aggravates it.

Fetal Hemoglobin↗
PubMed1994

Serum ferritin concentrations in transfusion dependent beta-thalassaemia.

Patients on a moderate red cell transfusion programme have iron overload where the concentrations of the serum ferritin were inappropriate to increases in the transfusion load as a result of limitations of apoferritin synthesis and conversion of ferritin into haemosiderin. This study confirms the limitations for the use of estimations of the serum ferritin to evaluate the iron status in patients with expected high overload as would be seen in patients on many years of maintenance red cell transfusions in the absence of iron chelation therapy. Poor compliance, inadequate dosage of Desferal (deferoxamine), and the late initiation of iron chelation therapy were factors that were considered in the patients with failure of response to iron chelation.

Blood Transfusion↗
PubMed1993

Tumorigenicity conferred to lymphoma mutant by major histocompatibility complex-encoded transporter gene.

Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules requires MHC-encoded molecules of the adenosine triphosphate binding cassette (ABC) family. Defects in these proteins represent a potential risk, since they are essential links in the machinery of T cell-mediated surveillance which continuously scrutinizes peptide samples of cellular proteins. Nevertheless, transfection of the mouse lymphoma mutant RMA-S with the rat ABC gene mtp2a (homologue to mouse HAM2 and human RING11), commonly termed TAP-2 genes, led to a marked increase in tumor outgrowth potential in vivo. This occurred despite restored antigen presentation and sensitivity to cytotoxic T lymphocytes, and was found to be due to escape from natural killer (NK) cell-mediated rejection. It has previously been proposed that adequate expression of self-MHC class I is one important mechanism to avoid elimination by NK cells. Our data argue that a defect in the machinery responsible for processing and loading of peptides into MHC class I molecules is sufficient to render cells sensitive to elimination by NK cells. The latter thus appear to function as a surveillance of the peptide surveillance machinery.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Hb E beta +-thalassaemia in west Malaysia: clinical features in the most common beta-thalassaemia mutation of the Malays [IVS 1-5 (G-->C)].

Patients with the Hb beta + [IVS 1-5 (G-->C)] clinically presented as beta-thalassaemia intermedia and remained asymptomatic in the absence of blood transfusions. With or without blood transfusions the patients were short and had moderate to marked thalassaemia facies. Children who received blood transfusions showed progressive iron loading with age. The serum ferritin and serum alanine transaminase levels were significantly raised in the patients who were given blood transfusions. In the presence of blood transfusions, and absence of adequate iron chelation therapy, splenectomy became an inevitable event at some stage of the disease because of increasing transfusing requirements.

Adolescent↗
PubMed1993

Spectrum of beta-thalassaemia mutations in transfusion dependent thalassaemia patients: practical implications in prenatal diagnosis.

The study concerned the identification of the beta-thalassaemia mutations that were present in 24 patients with beta-thalassaemia major who were transfusion dependent. The application of a modified polymerase chain reaction, the amplification refractory system (ARMS) was found to be an effective and rapid method for the identification of the beta-thalassaemia mutations. Six different mutations were detected. Seventy five percent of the patients were Chinese-Malaysians and showed the commonly occurring anomalies: 1. frameshift codon 41 and 42 (-TCTT); 2. the C to T substitution at position 654 of intron 2 (IVS-2); 3. the mutation at position -28(A to G); and the nonsense mutation A to T at codon 17. In the Malays, the common mutations seen were: 1. the G to C mutation at position 5 of IVS-1; 2. the G to T mutation at position 1 of intron 1 (IVS-1); and the A to T at codon 17. The delineation of the specific mutations present will enable effective prenatal diagnosis for beta-thalassaemia to be instituted.

Base Sequence↗
PubMed1993

Peripheral haemolysis, lipid peroxidation, iron status, and vitamin E in haemoglobin H syndromes in West Malaysia.

Following complete DNA characterisation patients with Hb H disease were assigned into two groups: deletional (alpha +/alpha o) and non deletional (HbCS/alpha o). Earlier studies have indicated that the group with (HbCS/alpha o) has more severe clinical problems. The serum malonyldialdehyde (MDA) levels, a secondary product of lipid peroxidation were within the normal range, though significantly higher levels of MDA were seen in the non-deletional type of Hb H disease when compared with the deletional type. Markedly low vitamin E levels were also seen in the former group. There were no significant differences in clinical severity may be attributed to an interplay of the accelerated destruction of damaged mature red blood cells secondary to the oxidative denaturation of Hb H and inclusion precipitation; higher levels of Hb H and more inclusion precipitation were seen in the group with (HbCS/alpha o). Low levels of vitamin E in the (HbCS/alpha o) group being due to its consumption in the neutralisation of free radicals formed with the oxidation of globin chains.

Adult↗
PubMed1993

Antibody to hepatitis C virus in thalassemia patients.

A specific enzyme immunoassay (EIA) for the diagnosis of hepatitis C virus (HCV) infection was developed by recombinant DNA technology. Abbott HCV EIA was used to detect antibody to HCV (anti-HCV) in non-transfused and multiply-transfused thalassemia patients. None of 11 non-transfused patients had anti-HCV but 3 of 52 (5.8%) multiply-transfused patients had anti-HCV. This study showed that the prevalence rate of HCV infection is low in thalassemia patients. However, it is still important to identify hepatitis C virus infected patients in high risk groups because hepatitis C is associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma.

Alanine Transaminase↗
PubMed1992

In vivo genotoxicity studies with p-benzoquinone dioxime.

P-Benzoquinone dioxime (BQD) appears to be a sex-specific rat carcinogen inducing tumours of the urinary bladder in female rats. The present paper shows that BQD is a direct-acting mutagen in Salmonella typhimurium TA98, confirming published data. In contrast to this in vitro data, negative results were obtained after oral administration of BQD to female rats in both the bone marrow micronucleus test and the in vivo liver UDS test. BQD did, however, induce a marked effect upon S-phase synthesis in the livers of female rats between 14 and 48 hr after a single oral dose of 250 mg/kg. A similar effect was also observed in the livers of male rats. There was no evidence of hepatotoxicity (in terms of elevated liver enzyme levels) after treatment of female rats with the compound indicating that the increase in cell proliferation was due to a direct mitogenic effect of BQD in this organ. Some liver mitogens have been found to be liver carcinogens; this does not appear to be the case for BQD. Nevertheless, the mitogenic activity of this compound might play a contributory role to the induction of bladder cancer in rats if it also acted as a mitogen in this tissue. Further studies are indicated, measuring genotoxicity and cell-proliferative activity in the bladder in order to further elucidate the mechanism of action of this compound as a rodent carcinogen.

Administration, Oral↗
PubMed1992

Late onset renal allograft anastomotic pseudoaneurysm with absent Doppler signal.

A large extrarenal pseudoaneurysm, originating from the arterial anastomosis of a renal allograft, occurred spontaneously 7 years after transplantation in a 29-year-old diabetic patient. Although the scintigraphic examination was diagnostic of a pseudoaneurysm, pulsed Doppler and color coded Doppler ultrasound failed to demonstrate a Doppler signal, suggesting erroneously a nonvascular fluid collection. The role of scintigraphy combined with duplex ultrasound in this rare but potentially fatal complication of renal transplantation is discussed.

Adult↗
PubMed1992

Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases.

In this study of 40 cases of basaloid squamous cell carcinoma, 83% arose in the pyriform sinus, base of tongue, tonsil, and larynx. The 35 men and five women ranged in age from 27 to 88 years (median 62). In patients for whom social habits were recorded, 24 of 26 patients were smokers and 22 of 25 drank ethanol. Most presented with stage III or IV disease. Twenty-seven patients had regional metastases at the time of presentation and 15 developed distant metastases. Seventeen patients died with disease (median survival 18 months). The tumors were composed of moderately pleomorphic basaloid cells forming nests, cords, and frequent cribriform patterns. Squamous dysplasia of surface mucosa, focal squamous differentiation within invasive basaloid squamous cell carcinoma, or foci of conventional squamous cell carcinoma were present, alone or in combination. All studied neoplasms were immunohistochemically positive for keratins with the 34 beta E12 antibody. Approximately 80% were immunoreactive using AE1/AE3 or CAM 5.2. Epithelial membrane antigen, carcinoembryonic antigen, and S100 protein were found in 83%, 53%, and 39%, respectively, of the cases. Diffuse, weak immunoreactivity for neuron-specific enolase was seen in 75% of tumors. Synaptophysin, chromogranin, muscle-specific actin, and glial fibrillary acidic protein were absent. Basaloid squamous cell carcinoma has been confused with adenoid cystic carcinoma and small cell undifferentiated carcinoma, but is usually distinguishable in routine hematoxylin and eosin-stained sections, or, in rare problematic cases, with the aid of immunohistochemical studies. Distinction is warranted because the biologic behavior of basaloid squamous cell carcinoma differs from that of both of these lesions.

Adult↗
PubMed1992

Molecular basis for membrane rigidity of hereditary ovalocytosis. A novel mechanism involving the cytoplasmic domain of band 3.

Hereditary ovalocytic red cells are characterized by a marked increase in membrane rigidity and resistance to invasion by malarial parasites. The underlying molecular defect in ovalocytes remained a mystery until Liu and colleagues (N. Engl. J. Med. 1990. 323:1530-38) made the surprising observation that the ovalocytic phenotype was linked to a structural polymorphism in band 3, the anion transporter. We have now defined the mutation in band 3 gene and established the biophysical sequelae of this mutation. This mutation involves the deletion of amino-acids 400-408 in the boundary between the cytoplasmic and the first transmembrane domains of band 3. The biophysical consequences of this mutation are a marked decrease in lateral mobility of band 3 and an increase in membrane rigidity. Based on these findings, we propose the following model for increased membrane rigidity. The mutation induces a conformational change in the cytoplasmic domain of band 3, leading to its entanglement in the skeletal protein network. This entanglement inhibits the normal unwinding and stretching of the spectrin tetramers necessary for membrane extension, leading to increased rigidity. These findings imply that the cytoplasmic domain of an integral membrane protein can have profound effects on membrane material behavior.

Amino Acid Sequence↗
PubMed1992

Types of thalassemia among patients attending a large university clinic in Kuala Lumpur, Malaysia.

We have identified the beta-thalassemia mutations in 59 patients with thalassemia major and 47 patients with Hb E-beta-thalassemia, and the deletional and nondeletional alpha-thalassemia determinants in 23 out of 24 patients with Hb H disease. All persons were attending the Haematology Clinic at the National University of Malaysia in Kuala Lumpur (Malaysia). Most patients (76) were of Malay descent, while 52 patients were Chinese, and two came from elsewhere. The most frequently occurring beta-thalassemia alleles among the Malay patients were IVS-I-5 (G----C) and G----A at codon 26 (Hb E), while a few others were present at lower frequencies. The Chinese patients carried the mutation characteristic for Chinese [mainly codons 41/42 (-TTCT) and IVS-II-654 (C----T)]; Malay mutations were not observed among Chinese and Chinese mutations were virtually absent in the Malay patients. The large group of patients with Hb E-beta-thalassemia and different beta-thalassemia alleles offered the opportunity of comparing hematological data; information obtained for patients with Hb E-beta-thalassemia living in other countries was included in this comparison. Twenty-three patients with Hb H disease carried the Southeast Asian (SEA) alpha-thalassemia-1 deletion; 13 had the alpha CS alpha (Constant Spring) nondeletional alpha-thalassemia-2 determinant, while the deletional alpha-thalassemia-2 (-3.7 or -4.2 kb) was present in 10 subjects. The --/alpha CS alpha condition appeared to be the most severe with higher Hb H values. Both deletional and nondeletional types of alpha-thalassemia-2 were seen among Malay and Chinese patients.

Academic Medical Centers↗
PubMed1992

Overexpression of the c-erbB-2 oncogene in sarcomas and small round-cell tumors of childhood. An immunohistochemical investigation.

Amplification and overexpression of the c-erbB-2 oncogene have been associated with a poor prognosis in breast cancer. The present study evaluates c-erbB-2 protein over-production in sarcomas and in small round-cell tumors of childhood by applying an immunohistochemical technique to formalin-fixed, paraffin-embedded tissues. This technique had previously demonstrated high sensitivity for the detection of c-erbB-2 activation. One peripheral neuroepithelioma demonstrated equivocal immunoreactivity for c-erbB-2 protein. There was no evidence of c-erbB-2 protein overproduction in 11 angiosarcomas, 21 chondrosarcomas, 10 epithelioid sarcomas, 14 Ewing's sarcomas, 20 hepatoblastomas, nine leiomyosarcomas, 12 liposarcomas, 13 malignant fibrous histiocytomas, nine malignant lymphomas, 15 neuroblastomas/ganglioneuroblastomas, 16 neurofibrosarcomas, 10 osteosarcomas, seven peripheral neuroepitheliomas, 10 rhabdomyosarcomas, six synovial sarcomas, and 20 Wilm's tumors. We conclude that overproduction of the c-erbB-2 protein is rare or absent in these neoplasms and that its detection is therefore not likely to be of practical utility in their pathologic evaluation and prognostication.

Bone Neoplasms↗
PubMed1991

Malignant mixed müllerian tumors: an immunohistochemical study of 47 cases, with histogenetic considerations and clinical correlation.

Forty-seven cases of malignant mixed müllerian tumors were reviewed histologically and studied immunohistochemically with three major objectives: to analyze the histogenetic relationship between the carcinomatous and sarcomatous components of these neoplasms, to ascertain the practical role of immunohistochemical studies in diagnosis and classification, and to determine the prognostic significance of immunohistochemically verified rhabdomyoblastic and neuroendocrine differentiation. Epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) was confirmed in all carcinomatous components; within the sarcomatous areas, it was identified among individual cells (60% of cases) and within poorly formed clusters of cells (57% of cases). There was a statistically significant tendency for concordant expression of alpha-1-antichymotrypsin, Leu-M1, S-100, Leu-7, and neuron-specific enolase between the carcinomatous and sarcomatous components of individual cases. These two findings provide evidence of common origin for the sarcomatous and carcinomatous components of these neoplasms. Histologic review of metastases in 21 cases revealed a biphasic composition in the majority of metastatic lesions (62%), another feature that further supports a common origin for the two components. From a practical standpoint, immunohistochemistry may be helpful in accentuating the biphasic pattern of these neoplasms and in verifying the presence of rhabdomyoblastic differentiation. In most cases, however, careful morphologic examination and thorough sampling will suffice for correct diagnosis and subclassification. The presence of heterologous, rhabdomyoblastic, or neuroendocrine differentiation did not have a statistically significant influence on survival; the last of these was associated with a tendency for a more rapidly fatal course.

Actins↗
PubMed1991

Evaluation of the in vivo genotoxicity of the structural analogues 2,6-diaminotoluene and 2,4-diaminotoluene using the rat micronucleus test and rat liver UDS assay.

The two structural isomers 2,4- and 2,6-diaminotoluene (DAT) differ in their carcinogenic properties; the 2,4-isomer is carcinogenic in rats and mice, whereas the 2,6-isomer has been reported to be non-carcinogenic. Both isomers were reported to be mutagenic in Salmonella typhimurium in the presence of S9, which was confirmed in the present study before in vivo assays were commenced. Both isomers were tested in the rat bone marrow micronucleus test and the rat liver UDS test to investigate how well these assays discriminate between the carcinogenic and the non-carcinogenic isomer. In the micronucleus test both isomers gave weakly positive results; however, with the carcinogen 2,4-DAT this weak effect was only detectable at very toxic doses and therefore the biological relevance of this result is questionable. Thus, the micronucleus test did not discriminate correctly between the carcinogen and the non-carcinogen. With the liver UDS test, discrimination was achieved but the positive effect seen for the carcinogenic isomer was weak and dependent on the method of preparation of the dosing suspensions. The results are discussed in relation to the carcinogenicity data on both compounds. It is concluded that although both isomers are potent genotoxins in vitro they exert their genotoxic potential only weakly in vivo and convincing discrimination between the carcinogenic and non-carcinogenic isomer was not demonstrated.

Animals↗
PubMed1991

Invasive Chrysosporium infection of the nose and paranasal sinuses in an immunocompromised host.

Aggressive fungal rhinosinusitis with Chrysosporium sp. occurred in a patient with acute lymphocytic leukemia. The infecting organism is an exceedingly rare human pathogen. Usually, human chrysosporial infections are mild and unmarked by symptoms. Most case reports appear in the pathology literature and describe the incidental finding of adiaspores in the pulmonary parenchyma at autopsy. Clinical disease from active growth of chrysosporial mycelia in human tissues has been noted on a porcine aortic valve prosthesis and in a tibial abscess. Hyphal elements were not recovered from any other body parts of these patients. Histopathologic and microbiologic studies permitted the identification of this rarely encountered organism. Our patient experienced systemic spread of Chrysosporium organisms. Treatment of this pathogen is the same as for other opportunistic fungal infections.

Adolescent↗
PubMed1991

Quantifying the spread of botulinum toxin through muscle fascia.

Botulinum toxin was recently approved for treating several head and neck dystonias. Paralysis of neighboring muscles is the major complication of its use. Spread of toxin from the injected muscle has been suggested as an etiology. This study examines how botulinum toxin crosses muscle fascia by a novel method of quantifying muscular paralysis. Botulinum toxin (0.2 to 10 U) was placed onto the fascia of rat tibialis anterior (TA) muscles (n = 6). Toxin was also placed on dose-matched muscles that had their fascia surgically removed (n = 6). Twenty-four hours later, the nerve to the tibialis anterior was electrically stimulated to deplete the muscle fibers of glycogen. Toxin-paralyzed fibers retained their glycogen and appeared purple on periodic acid-Schiff (PAS) stain. Botulinum toxin easily passed through muscle fascia even at subclinical doses. The presence of fascia reduced the spread of botulinum toxin by 23%. These results suggest that spread of botulinum toxin can be prevented only by delivering small doses to the center of a target muscle.

Animals↗