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Biomedical subjects

S Mathew

Publications and source records attributed to S Mathew.

At least 19 recordsLinked to original sources
PubMed2001

Differential regulation of the fibroblast growth factor (FGF) family by alpha(2)-macroglobulin: evidence for selective modulation of FGF-2-induced angiogenesis.

The fibroblast growth factor (FGF) family has an important role in processes such as angiogenesis, wound healing, and development in which precise control of proteinase activity is important. The human plasma proteinase inhibitor alpha(2)-macroglobulin (alpha(2)M) regulates cellular growth by binding and modulating the activity of many cytokines and growth factors. These studies investigate the ability of native and activated alpha(2)M (alpha(2)M*) to bind to members of the FGF family. Both alpha(2)M and alpha(2)M* bind specifically and saturably to FGF-1, -2, -4, and -6, although the binding to alpha(2)M* is of significantly higher affinity. Neither alpha(2)M nor alpha(2)M* bind to FGF-5, -7, -9, or -10. FGF-2 was chosen for more extensive study in view of its important role in angiogenesis. It was demonstrated that FGF-2 binds to the previously identified TGF-beta binding site. The alpha(2)M* inhibits FGF-2-dependent fetal bovine heart endothelial cell proliferation in a dose-dependent manner. Unexpectedly, alpha(2)M* does not affect FGF-2-induced vascular tubule formation on Matrigel basement membrane matrix or collagen gels. Further studies demonstrate that FGF-2 partitions between fluid-phase alpha(2)M* and solid-phase Matrigel or collagen. These studies suggest that the ability of alpha(2)M* to modulate the activity of FGF-2 is dependent on an interplay with extracellular matrix components. (Blood. 2001;97:3450-3457)

Animals↗
PubMed2001

Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia.

In childhood B-lineage acute lymphoblastic leukemia (ALL), the most common genetic change, the ETV6-CBFA2 (TEL-AML1) fusion resulting from the cryptic t(12;21)(p13;q22) is associated with a favorable outcome. Therefore, it is important to identify patients with this translocation so that they can receive appropriate treatment. To identify new partner breakpoints for ETV6 and CBFA2, we selected 30 patients with childhood ALL in whose leukemic cells a t(12;21) had been detected by RT-PCR. Conventional cytogenetics revealed that 12p abnormalities were present in 10 patients and that other random abnormalities were present in another 15, including 9 with a numerical or structural abnormality of chromosome 21. Normal karyotypes were observed in the leukemic blasts of five patients. Interphase fluorescence in situ hybridization (FISH) confirmed the RT-PCR finding of the t(12;21) in each patient and detected the loss of the wild-type ETV6 allele in 14 (47%) patients. Metaphase cells from only 20 patients were available for additional FISH analysis. In 13 patients, the expected fusion signal of t(12;21) was observed on der(21)t(12;21), and the reciprocal CBFA2 signal was observed on der(12)t(12;21). However, in six patients with the ETV6-CBFA2 fusion on chromosome 21, the reciprocal CBFA2 signal was observed not on 12p13 but on 4q21, 4q27, 8q24, 11q24, 14q11.2, or 16p13.1. In four of these six patients, we found interstitial insertions of part of CBFA2. In another patient, the ETV6-CBFA2 fusion was observed on 4q21 rather than on 21q. Thus, seven (35%) of the 20 patients with a t(12;21) revealed complex rearrangements. Our findings also indicate the importance of analyzing metaphase chromosomes in identifying cryptic and complex rearrangements involving ETV6 and CBFA2.

Adolescent↗
PubMed2001

Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals.

Decreased expression of the epithelial cell adhesion protein E-Cadherin occurs in several forms of human epithelial-derived cancers, including bladder cancers. We investigated the possibility that aberrant methylation of the CpG island flanking the 5' transcriptional start site of the e-cadherin gene is responsible for the decreased expression of this gene in bladder cancer, similar to the relationship previously seen between e-cadherin methylation and gene expression in other types of human cancers. Using methylation-specific polymerase chain reaction, we found methylation of this CpG island in 20 of 47 cases (43%) of bladder neoplasms ranging from low-grade papillary neoplasms to advanced, invasive cancers. When methylation status was compared to immunochemical staining for E-Cadherin, we found significantly diminished levels of E-Cadherin expression in 14 of 15 cases (93%) with methylation of the gene. We also found decreased expression of E-Cadherin, although to a somewhat lesser extent, in a high percentage (77%) of the cases without methylation of the gene. Although these data suggest a relationship between e-cadherin CpG island methylation and decreased gene expression, it evident that other mechanisms also contribute to decreased expression of this gene in bladder neoplasia. Remarkably, we also found low levels of e-cadherin methylation in urothelial cells from three of nine (33%) histologically normal bladders, with all three of the normal bladder samples with methylated e-cadherin being from individuals older than 70 years of age. Thus, methylation of the e-cadherin CpG island may occur normally in this tissue with aging as well as in low-grade papillary neoplasms, and is not specific to cancer in the bladder. This finding of methylation in normal urothelial cells from elderly individuals is provocative with respect to a possible link between aging and increased risk for bladder cancer, but it suggests limitations on the usefulness of using methylation of e-cadherin as a molecular marker for detection of bladder cancer.

Adult↗
PubMed2001

Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia.

We used a recently described molecular cytogenetic method, spectral karyotyping (SKY), to analyze metaphase chromosomes from 30 pediatric patients with acute lymphoblastic leukemia (ALL). This group included 20 patients whose leukemic blast cells lacked chromosomal abnormalities detected by conventional cytogenetics and 10 patients whose blast cells had multiple chromosomal abnormalities that could not be completely identified by G-banding analysis. In two of the 20 patients (10%) with apparently normal karyotypes, SKY identified three cryptic translocations: a t(7;8)(q34-35;q24.1) in one patient and a t(13;17)(q22;q21) and a der(19)t(17;19)(q22;p13) in another. Fluorescence in situ hybridization using subtelomeric probes proved the latter translocation to be a t(17;19). SKY analysis was also successful in defining the nature of the chromosomal abnormalities in four of the 10 patients with marker and derivative chromosomes. The identified abnormalities in the latter group included three novel translocations: a der(X)t(X;5)(p11.4;q31), a der(21)t(X;21)(p11.4;p11.2) and a t(X;9)(p11.4;p13). The presence of the t(X;9) was suggested by conventional cytogenetics. The application of fluorescence in situ hybridization using chromosome-specific painting probes and locus-specific probes complemented the SKY analysis by confirming the nature of the chromosome rearrangements defined by SKY and by identifying the amplification of the AML1/CBFA2 gene in one patient with a duplicated 21q. Our study demonstrates the utility of SKY in identifying novel translocations and in refining the identity of chromosomal abnormalities in leukemias.

Adolescent↗
PubMed2001

Use of vancomycin in the culture of Mycobacterium tuberculosis from gastric lavage.

BACKGROUND & OBJECTIVES: Earlier studies from the Tuberculosis Research Centre, Chennai, on culture of Mycobacterium tuberculosis from gastric lavage (GL) specimens in selective Kirchner's medium (SK) resulted in a loss of 60 per cent culture results due to contamination with aerobic spore bearers (ASB). Addition of vancomycin to SK (SKV) effectively reduced the contamination rate to 20 per cent. The objective of the present study was to further reduce the contamination by collecting the specimens in bottles containing vancomycin, thus providing continuous exposure of the sample to the drug, which is bactericidal to ASB. METHODS: One thousand GL specimens collected from children in vancomycin containing bottles were decontaminated and cultured in SK medium, with and without vancomycin, subcultured on Lowenstein Jensen (LJ) medium and the culture results compared. RESULTS: The contamination of cultures in SK and SKV was 15 and 4 per cent respectively when the specimens were collected in bottles containing vancomycin compared to 60 and 20 per cent contamination reported in the earlier studies. INTERPRETATION & CONCLUSION: The reduced contamination in SK and SKV is most likely due to the collection of samples in vancomycin containing bottles. Although a concurrent comparison of samples processed in vancomycin free conditions would have been ideal, it could not be done due to practical difficulties. The study thus confirms the value of vancomycin as a major deterrent for contamination due to aerobic spores and better results can be obtained if vancomycin is used in sample collection bottles, transport media and liquid culture media used in mycobacteriology laboratories particularly in humid and tropical environment.

Culture Media↗
PubMed2001

Training status influences T-cell responses in women following acute resistance exercise.

The purpose of this investigation was to examine white blood cell counts (WBC), immunoglobulin (IgA, IgG, IgM) levels, and T-cell proliferation following acute resistance training in 9 untrained (UT) and 6 trained (TR) women. Resistance training on 7 Universal machines at the subject's 10 repetition maximum (IORM) was performed at 89 +/- 5% for UT and 88 +/- 3% for TR. Blood was analyzed for WBCs and Ig levels pre-exercise, immediately postexercise, and 1.5, 3, and 24 hours postexercise. T-cell proliferation was determined pre-exercise and 3 hours postexercise through response to phytohemagglutanin (PHA). WBCs were significantly elevated in the UT subjects 1.5 and 3 hours postexercise compared with pre- and immediately postexercise; no differences (p < 0.05) were observed in TR subjects. No significant differences were found for Ig levels either between or within groups, although there was a trend for decreased IgG following exercise. T-cell proliferation was significantly decreased in the UT at 3 hours postexercise (0.27 +/- 0.06 units) compared with pre-exercise (0.41 +/- 0.06 units), whereas the proliferative response in TR was not significantly different from pre-exercise (0.48 +/- 0.04 units) to 3 hours postexercise (0.34 +/- 0.06 units). These data indicate that UT subjects experience an increase in WBC counts and a decrease in T-cell proliferative ability after acute resistance training, whereas TR subjects experience no significant change in these parameters.

Adult↗
PubMed2000

Trisomy of the long arm of chromosome 1 resulting in a dicentric derivative (6)t(1;6) chromosome in a child with myelodysplastic syndrome following treatment for a primitive neuroectodermal tumor.

We report the clinical, hematologic, and cytogenetic findings for a child with secondary myelodysplastic syndrome (MDS) after treatment for a primitive neuroectodermal tumor. At the time of conversion to MDS, conventional cytogenetics revealed an unbalanced der(6)t(1;6) that resulted in trisomy of the long arm of chromosome 1 and partial monosomy and duplication of 6p. Using alpha satellite probes, fluorescence in situ hybridization of bone marrow cells showed that the rearranged chromosome contained the centromeres of both chromosomes 1 and 6, thus forming a dic(1;6) resulting in trisomy 1q. This report is the first to describe a case of childhood secondary myelodysplastic syndrome associated with a trisomy 1q involving chromosome 6.

Brain Neoplasms↗
PubMed2000

Direct drug susceptibility test for tubercle bacilli by the sputum swab culture method.

OBJECTIVE: To develop a simple, inexpensive method for testing direct drug susceptibility of tubercle bacilli to isoniazid (INH) and streptomycin (SM) which can be adopted for use even in remote parts of the world. DESIGN: Using 239 smear-positive sputum specimens obtained from an equal number of patients, a comparison was made between the direct swab susceptibility test and the standard indirect method for INH and SM using Löwenstein-Jensen (L-J) medium. RESULTS: There was 95% agreement of results for INH by 6 weeks and 90% for SM by 8 weeks; 96% of INH-resistant cultures could be detected in 5 weeks and 91% of SM-resistant cultures by 8 weeks. The discrepancies in the two tests were virtually symmetrically distributed at 6 and 8 weeks. The speed and efficiency of detection of resistance by the swab method was also assessed in relation to the standard indirect method. For INH, 96% of the cultures were detected by the fifth week, while 66% were detected as early as 2 weeks and 93% by 4 weeks. With SM, 84% were detected by 4 weeks, 89% by 5 weeks and 91% by 8 weeks. CONCLUSION: This study has indicated the usefulness of the swab method for testing the drug susceptibility of tubercle bacilli. As this method is simple and easy, and does not even require a centrifuge, it has the potential of application even in the remote parts of the world. The material used, Cetavlon (Cetrimide), is inexpensive and easily water soluble, and more importantly, aqueous solutions are self-sterilizing. It should be stressed, however, that the results obtained with this test take the same time as conventional methods, and it can therefore not be considered as a rapid test.

Antibiotics, Antitubercular↗
PubMed2000

Concurrent translocations of MLL and CBFA2 (AML1) genes with new partner breakpoints in a child with secondary myelodysplastic syndrome after treatment of acute lymphoblastic leukemia.

The MLL gene at 11q23 is frequently disrupted by chromosomal translocations in de novo acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), and in secondary leukemia induced by treatment with inhibitors of topoisomerase II, including the epipodophylotoxins. The CBFA2 gene at 21q22 is also frequently disrupted in de novo ALL and AML and less commonly in secondary AML. Rearrangements of MLL and CBFA2 have been described in de novo and secondary myelodysplastic syndrome (MDS). There have been no previous descriptions of coexisting abnormalities of MLL and CBFA2 in cases of MDS or acute leukemia. We describe a patient who developed secondary MDS after chemotherapy for hyperdiploid ALL. At the time of conversion to MDS, the patient had 46 chromosomes, with an 11q23/MLL translocation involving a new partner breakpoint at 2p23 and a 21q22/CBFA2 translocation involving a new partner breakpoint at 6p22. This report is the first to describe new partner breakpoints at 2p23 and 6p22 for MLL and CBFA2 genes, respectively, and concurrent rearrangements of these genes in a patient with secondary MDS.

Child, Preschool↗
PubMed1999

Identification of a novel cardiac lineage-associated protein(cCLP-1): A candidate regulator of cardiogenesis.

We describe the isolation and characterization of a cDNA clone, called cCLP-1, that is a candidate for the previously described early cardiac-specific transcription factor BBF-1. BBF-1 binds the MEF2 (or element B) binding site within the cardiac myosin light chain 2 (MLC2) gene promoter. We used the element B sequence as a probe to screen an expression library constructed from mRNA obtained from the presumptive heart-forming regions of stage 6 chicken embryos. This yielded the cCLP-1 cDNA clone. Gel-shift analysis of stage 6 embryonic chicken protein extracts suggests that a protein that is recognized by the anti-cCLP-1 antibody binds to the same element B binding site to which BBF-1 binds. cCLP-1 mRNA was detected early in chicken development, prior to cardiac fate assignment at stage 4. The expression pattern of cCLP-1, based on whole mount in situ hybridization, coincides remarkably well with the established morphogenetic field of early heart formation. The nuclear localization of cCLP-1 is phosphorylation-dependent, suggesting that cCLP-1 may be a member of that class of transcription factors whose activity is regulated by cytoplasm to nucleus transport. Taken together, these data suggest that cCLP-1 may encode a novel transcription factor whose expression pattern is in agreement with that of the cardiogenic precursor cells of the early chicken embryo.

Amino Acid Sequence↗
PubMed1999

Reduced folate carrier expression in acute lymphoblastic leukemia: a mechanism for ploidy but not lineage differences in methotrexate accumulation.

Methotrexate (MTX) is one of the most active and widely used agents for the treatment of acute lymphoblastic leukemia (ALL). To elucidate the mechanism for higher accumulation of MTX polyglutamates (MTX-PG) in hyperdiploid ALL and lower accumulation in T-lineage ALL, expression of the reduced folate carrier (RFC) was assessed by reverse transcription-polymerase chain reaction in ALL blasts isolated from newly diagnosed patients. RFC expression exhibited a 60-fold range among 29 children, with significantly higher expression in hyperdiploid B-lineage ALL (median, 11.3) compared with nonhyperdiploid ALL (median, 2.1; P <.0006), but no significant difference between nonhyperdiploid B-lineage and T-lineage ALL. Furthermore, mRNA levels of RFC (mapped by FISH to chromosome 21) were significantly related to chromosome 21 copy number (P =.0013), with the highest expression in hyperdiploid ALL blasts with 4 copies of chromosome 21. To assess the functional significance of gene copy number, MTX-PG accumulation was compared in ALL blasts isolated from 121 patients treated with either low-dose MTX (LDMTX; n = 60) or high-dose MTX (HDMTX; n = 61). After LDMTX, MTX-PG accumulation was highest in hyperdiploid B-lineage ALL with 4 copies of chromosome 21 (P =.011), but MTX-PG accumulation was not significantly related to chromosome 21 copy number after HDMTX (P =.24). These data show higher RFC expression as a mechanism for greater MTX accumulation in hyperdiploid B-lineage ALL and indicate that lineage differences in MTX-PG accumulation are not due to lower RFC expression in T-lineage ALL.

Carrier Proteins↗
PubMed1999

Lymphoid lesions of the parotid.

Lymphoid lesions of the parotid gland are much less common than their epithelial counterparts, and thus cytologic experience on fine-needle aspiration (FNA) is limited. FNA of lymphoid lesions with ancillary aids (flow cytometry and immunophenotypic studies) can make a definitive diagnosis. All FNAs of the parotid gland performed at the Johns Hopkins Hospital in an 8-yr span (1990-1998) were reviewed retrospectively. In all, 391 cases were done, of which 76 cases of lymphoid lesions were identified. The relevant cytology, histology, and flow cytometry were analyzed. Of the 76 lymphoid lesions, results included reactive lesions (n = 35), lymphoepithelial cysts (n = 27), malignant lymphomas (n = 12), an atypical lymphoid population (n = 1), and Sjogren's disease (n = 1). We conclude that both reactive and malignant lymphoid lesions of the parotid can be diagnosed on FNA with adjunctive tests such as flow cytometry and immunophenotyping, obviating the need for surgery. Diagn. Cytopathol. 1999;21:170-173.

Biopsy, Needle↗
PubMed1999

Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia.

The t(12;21)(p13;q22) is a cryptic abnormality observed in 25% of children with B-lineage acute lymphoblastic leukemia (ALL), associated with a favorable prognosis. To determine whether specific cytogenetic abnormalities accompany the t(12;21), we analyzed the cytogenetic profiles of blast cells from 169 ALL cases positive for the t(12;21), previously identified by molecular methods. Only 13.6% of samples had normal karyotypes. Structural changes were detected in 89.7% of abnormal karyotypes, and numerical abnormalities in 47%. Rearrangements of 12p were the most frequent structural aberration (57 out of 146 patients with chromosomal abnormalities). Nonspecific deletions of chromosomes 6 and 9 were also found. The most frequent numerical abnormalities was trisomy for chromosomes 21. Blast cells were pseudodiploid (45.6%), hyperdiploid with 47 to 51 chromosomes (24.3%), hypodiploid with 44 to 45 chromosomes (10%), near-triploid (0.6%), or near-tetraploid (5.9%). Our results show that the t(12;21) is not associated with hyperdiploidy of 52 to 68 chromosomes or with the prognostic t(1;19), t(4;11) or t(9;22). Only children with B-lineage ALL who lack these abnormalities detected by conventional cytogenetics will probably benefit from additional testing by molecular methods to detect the t(12;21).

Child↗
PubMed1999

Comparison of cytogenetics, Southern blotting, and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in children with acute leukemia and with 11q23 abnormalities.

Bone marrow samples from 67 children with acute leukemia and with cytogenetic evidence of chromosome 11 band q23 (11q23) abnormalities were characterized by fluorescence in situ hybridization (FISH) and Southern blot analysis to determine whether FISH could reliably detect MLL gene rearrangements in this population. Among the 42 patients with acute lymphoblastic leukemia (ALL), MLL gene rearrangements were detected in cells from 23 patients (54.8%) by both FISH and Southern blot analysis. FISH identified allelic deletions of MLL gene in five of 12 patients (42%) with ALL and with deletion of 11q23. In 22 of 25 children (88%) with AML, FISH detected MLL gene rearrangements, whereas Southern blot analysis identified rearrangements in 24 of 25 patients (96%). For children with acute leukemia and with 11q23 abnormalities, we recommend that FISH be used for the rapid screening of MLL gene rearrangements and that Southern blot analysis be used for the definitive assessment of the MLL gene status.

Acute Disease↗