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M A Iqbal

Publications and source records attributed to M A Iqbal.

At least 19 recordsLinked to original sources
PubMed2006

Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system.

Biphenotypic acute leukemia (BAL) is a rare, difficult to diagnose entity. Its identification is important for risk stratification in acute leukemia (AL). The scoring proposal of the European Group for the Classification of Acute Leukemia (EGIL) is useful for this purpose, but its performance against objective benchmarks is unclear. Using the EGIL system, we identified 23 (3.4%) BAL from among 676 newly diagnosed AL patients. Mixed, small and large blast cells predominated, with FAB M2 and L1 constituting the majority. All patients were positive for myeloid (M) markers and either B cell (B) (17 or 74%) or T cell (T) (8 or 34%) markers with two exceptional patients demonstrating trilineage phenotype. Six (50%) of studied M-B cases were positive for both IGH and TCR. In six (26%) patients myeloid lineage commitment was also demonstrable by electron cytochemistry. Abnormal findings were present in 19 (83%) patients by cytogenetics/FISH/molecular analysis as follows: t(9;22) (17%); MLL gene rearrangement (26%); deletion(6q) (13%); 12p11.2 (9%); numerical abnormalities (13%), and three (13%) new, previously unreported translocations t(X;6)(p22.3;q21); t(2;6)(q37;p21.3); and t(8;14)(p21;q32). In conclusion, the EGIL criteria for BAL appear robust when compared against molecular techniques that, if applied routinely, could aid in detecting BAL and help in risk stratification.

Acute Disease↗
PubMed2000

FISH analysis in chromophobe renal-cell carcinoma.

Loss of chromosomes 1, 2, 6, 10, 13, 17, and 21 is a characteristic finding in chromophobe renal-cell carcinoma (ChRCC). Previously, cytogenetic and molecular genetic techniques were used in demonstrating the chromosomal monosomies in ChRCCs. We performed interphase fluorescent in situ hybridization (FISH) using centromeric probes for chromosomes 1, 2, 6, and 10 on touch imprint smears from six histologically proven ChRCCs. All six ChRCC tumors showed one FISH signal corresponding to one copy number for each of these chromosomes. The percent cells with one FISH signal ranged from 48-88% (chromosome 1), 36-89% (chromosome 2), 26-98% (chromosome 6), and 64-99% (chromosome 10). In addition, 3 of the 6 cases were further studied with centromeric probes for chromosomes 13, 17, and 21. All three revealed monosomy of these three chromosomes. We conclude that interphase FISH performed on touch imprint smears is a relatively simple, rapid, and reliable method for detecting chromosome abnormalities which are specific for ChRCCs.

Carcinoma, Renal Cell↗
PubMed1999

Fine-needle aspiration biopsy diagnosis of small round cell tumors of childhood: A comprehensive approach.

Fine-needle aspiration biopsy findings in small round cell malignant tumors of children are briefly reviewed. All of these tumors usually have characteristic cytomorphology which, when recognized, may lead to a definitive diagnosis. However, when these tumors are undifferentiated, morphologic criteria may not be sufficient for arriving at a correct diagnosis. A variety of ancillary studies including electron microscopy, immunohistochemistry and DNA ploidy, cytogenetics, and fluorescent in situ hybridization may provide valuable additional information for precise characterization of these neoplasms. Some of the ancillary studies may also be used for assigning these cases to prognostically significant subgroups. This information may also help in defining the most suitable chemotherapeutic regimens for these tumors. Since most of these special studies require only a small amount of cellular material, fine-needle aspiration biopsy is ideally suited for obtaining samples for these procedures. It is hoped that as cytogenetic and molecular techniques become available in many diagnostic laboratories, a comprehensive evaluation of aspiration biopsies from round cell malignant tumors, encompassing a precise pathologic diagnosis, determination of prognosis, and prediction of response to therapy, will be possible in a majority of cases. Diagn. Cytopathol. 1999;21:81-91.

Biopsy, Needle↗
PubMed1999

Use of FISH technique in the diagnosis of chromosomal syndromes.

Major chromosome abnormalities are present in 0.65% of all neonates. Fluorescent in situ hybridization (FISH) is useful in diagnosing microdeletion syndromes that would otherwise be difficult to diagnose using standard cytogenetics. In this study, we used FISH analysis in the laboratory diagnosis of 4 patients with Prader-Willi Syndrome [del(15)(q11.2q12)], 4 patients with DiGeorge syndrome [del(22)(q11.2q11.23)] and 4 patients with Williams syndrome [del(7)(q11.23q11.23)]. High-resolution chromosome analysis in all these patients was either normal or inconclusive but all the syndromes were confirmed using FISH. We recommend cytogenetic analysis should always be supplemented with FISH to diagnose all cases suspected of a microdeletion syndrome.

Adolescent↗
PubMed1997

A case of presumptive monosomy 21 re-diagnosed as unbalanced t(5p;21q) by FISH and review of literature.

By using fluorescence in situ hybridization (FISH), we demonstrate a case of monosomy 21 to result from an unbalanced translocation involving the short arm of chromosome 5 and the long arm of chromosome 21. Our case is compared to 3 similar cases of t(5p;21q) reported recently, which were also originally diagnosed as monosomy 21. The breakpoint on chromosome 5 in these cases occurred in the p13-p15 region, whereas the breakpoint on chromosome 21 was in the q21-q22 region. Comparison of the clinical findings in these patients demonstrated great similarities. Furthermore, a strong correlation between the clinical manifestations of these patients with cridu-chat syndrome patients was also noted. We suggest that cases with unbalanced t(5p;21q) represent a distinct syndrome which can be grouped under a new category of "5p/21q deletion syndrome."

Chromosomes, Human, Pair 21↗
PubMed1996

Cytogenetic findings in renal cell carcinoma.

Cytogenetic characterization of 24 renal cell carcinomas (RCCs) was performed. The various RCC subtypes included 8 chromophobe RCCs, 12 nonpapillary RCCs, and 4 papillary RCCs. Loss of chromosomes 1, 2, 6, 10, and 17 were observed in 5 of 8 chromophobe RCCs. Five of the 12 nonpapillary RCCs showed abnormalities involving chromosome 3. These were deletion of the 3p13 region, loss of the whole chromosome 3, and unbalanced translocation resulting in a derivative. Of the 4 papillary RCCs, two showed trisomy 7 and 17 along with other abnormalities, one had trisomy for chromosomes 7, 12, and 13, along with loss of chromosome #5 and Y chromosomes, and another papillary RCC revealed trisomy 15 and trisomy 17. These results further show that specific cytogenetic abnormalities are associated with various subtypes of RCCs.

Adult↗
PubMed1993

Identification of a chymotrypsin-like mast cell protease in rat brain capable of generating the N-terminus of the Alzheimer amyloid beta-protein.

Cleavage after Met596 of the beta-amyloid precursor protein to generate the N-terminus of beta-protein indicates the activity of a protease having chymotrypsin-like specificity. A chymotrypsin-like protease is further implicated in Alzheimer's disease by the increased synthesis of the protease inhibitor alpha 1-antichymotrypsin in pathologically affected brain regions and by the presence in the amyloid deposits of inactivated forms of alpha 1-antichymotrypsin (indicating irreversible binding to a target chymotrypsin-like protease). In the present report, we have purified from rat brain a chymotrypsin-like protease that (a) binds with high affinity to human alpha 1-antichymotrypsin, (b) proteolytically generates a beta-protein-containing C-terminal fragment from full-length recombinant human beta-amyloid precursor protein, and (c) selectively cleaves methoxysucinyl-Glu-Val-Lys-Met- p-nitroanilide (a substrate modeling the protease recognition domain for the beta-protein N-terminal cleavage site). Amino acid sequences of tryptic fragments of the purified rat brain chymotrypsin-like protease indicate an identity with rat mast cell protease I. Moreover, the ontogeny and compartmentalization of rat brain chymotrypsin-like protease are consistent with those of connective tissue-type mast cells in the meningeal and intracortical perivasculature. Because these areas in human brain form extensive beta-amyloid deposits in Alzheimer's disease, Down's syndrome, and hereditary cerebral hemorrhage with amyloidosis of Dutch origin, the present findings suggest that a brain mast cell chymotrypsin-like protease may participate in generating perivascular beta-protein, which ultimately aggregates into beta-amyloid deposits.

Alzheimer Disease↗
PubMed1991

An ELISA assay for GAP-43.

An ELISA assay for the growth associated protein GAP-43 was developed to determine rapidly its relative abundance in neuronal tissue. The assay was performed with affinity-purified anti-GAP-43 antibody that detected a single band of Mr = 42,000-45,000 on Western blots of rat brain homogenates but no bands on blots of liver homogenates. GAP-43 was determined by ELISA assay in as little as 0.6 microgram protein of brain homogenate. The assay was highly reproducible; the standard error of the mean of sample to sample variation was less than 5%. When ELISA development time was held constant, the standard error of the mean of inter-assay variation was between 2 and 7%. Using this method, GAP-43 immunoreactivity was examined in developing rat brain. At post-natal day 1, GAP-43 immunoreactivity was 3-4 times greater than that observed in the adult, remained elevated for several weeks, and decreased by the end of the first month of life. These results are in accord with previous studies on the expression or synthesis of GAP-43 during neuronal development.

Animals↗
PubMed1989

A human adult Wilms' tumor. Histologic, ultrastructural, and cytogenetic analysis.

The cytogenetic, histologic, and electron microscopic studies of an adult patient with Wilms' tumor are presented. Wilms' tumor (nephroblastoma) is a common renal tumor of childhood but is extremely rare in people over 15 years old. The histologic analysis of the patient's tumor, including both light and electron microscopic analysis, indicated that this tumor satisfies the histologic criteria for an adult Wilms' tumor, namely, blastemic cells that are immature renal parenchymal cells, embryonic tubular structures, and a scanty stromal component consisting of loosely arranged spindle cells. The tumor showed several ultrastructural features characteristic of adult Wilms' tumor, namely, markedly elongated mitochondria, autophagic vacuoles, and intracytoplasmic filaments. Karyotypic analysis was performed on the patient's peripheral leukocytes and tumor cells. The leukocytes showed no significant increase in gaps and breaks, and the patient appears to have a normal male karyotype. Some interesting chromosomal anomalies were observed in the cultured tumor cells: at least one chromosome 13, both chromosomes 22, and the X chromosome are missing, three markers are present, and there is a possible deletion of 12p.

Chromosome Aberrations↗
PubMed1988

Replication program of active and inactive multigene families in mammalian cells.

In a comprehensive study, the temporal replication of tissue-specific genes and flanking sequences was compared in nine cell lines exhibiting different tissue-specific functions. Some of the rules we have determined for the replication of these tissue specific genes include the following. (i) Actively transcribed genes usually replicate during the first quarter of the S phase. (ii) Some immunoglobulin genes replicate during the first half of S phase even when no transcriptional activity is detected but appear to replicate even earlier in cell lines where they are transcribed. (iii) Nontranscribed genes can replicate during any interval of S phase. (iv) Multigene families arranged in clusters of 250 kilobases or less define a temporal compartment comprising approximately one-quarter of S phase. While these rules, and others that are discussed, apply to the tissue-specific genes studied here, all tissue-specific genes may not follow this pattern. In addition, housekeeping genes did not follow some of these rules. These results provide the first molecular evidence that the coordinate timing of replication of contiguous sequences within a multigene family is a general property of the mammalian genome. The relationship between replication very early during S phase and the transcriptional activity within a chromosomal domain is discussed.

Animals↗
PubMed1987

Replication of proto-oncogenes early during the S phase in mammalian cell lines.

Members of several classes of proto-oncogenes replicate during the first third of S-phase in two human (K562 erythroleukemia and HeLa), one Chinese hamster (CHO) and eight mouse cell lines. These cell lines exhibit a variety of specialized functions characteristic of pre-B and B cells, T cells and erythroid cells. The proto-oncogenes studied include fos, myc, myb, abl, fes, fms, mos, raf, rel, sis, Ha-ras, Ki-ras, and N-ras. In K562 cells, amplified and rearranged c-abl genes show a pattern of temporal replication during S that is similar to the pattern observed for the 5' breakpoint cluster region (bcr) and the amplified C lambda light chain immunoglobulin genes. The c-Ki-ras related sequences in CHO cells provide one example of late replicating proto-oncogene sequences that are present in multiple copies. The cellular gene N-myc replicates late during S in some of these cell lines. In three pre-B cell lines in which N-myc specific transcripts have been detected, N-myc replicates earlier in the S phase than in the other cell lines studied here.

Animals↗
PubMed1987

Ring chromosome 6: report of a patient and literature review.

A patient with ring chromosome 6 had most of the manifestations previously reported in this syndrome and also had albinoid fundi and unilateral aniridia, findings not previously described. In most peripheral leukocyte metaphases analyzed, one chromosome 6 was replaced by a monocentric ring chromosome with deletion of the 6p and 6q. Fifteen other patients with a ring chromosome 6 have been reported. The most frequent findings were mental retardation, prenatal and postnatal failure, epicanthal folds, flat nasal bridge, short neck, apparently low-set and/or malformed ears, microphthalmia, and micrognathia. Studies of coagulation Factors XII and XIII and of the P blood group for possible assignment on distal 6p and 6q did not provide evidence for localization of the genes for these factors on the pter----p24 part of chromosome 6.

Chromosome Aberrations↗
PubMed1987

Partial duplication 16q: report of two affected siblings resulting from a maternal translocation and literature review.

Two siblings with a partial duplication 16q, born to a woman with a balanced translocation (6;16), are described. The first infant died at 8 weeks of age; the second died at 4 months. Fifteen other cases of duplications involving 16q have been reported, all of them derived from a balanced parental translocation. The most frequent physical findings have included dysmorphic facies characterized by high forehead, prominent nose, antimongoloid slant, malformed ears, and micrognathia, as well as flexion contractures of the joints, deformity of the feet, and genital hypoplasia in the male. Anorectal, intestinal and cardiac malformations were less frequent findings. Most of the affected infants died at ages ranging from 8 days to 6 months. The few with longer survival (up to 6 years) had a shorter, more distal segment duplication of chromosome 16. Although intrauterine growth retardation and microcephaly were not always present at birth, most of the infants had postnatal growth failure. The phenotypic and clinical findings of the two infants in this report are compared with those of previously reported cases, from which there appears to be correlation of the length of the 16q duplication with clinical phenotype and survivals.

Abnormalities, Multiple↗
PubMed1987

Rate of replication of the murine immunoglobulin heavy-chain locus: evidence that the region is part of a single replicon.

We measured the temporal order of replication of EcoRI segments from the murine immunoglobulin heavy-chain constant region (IgCH) gene cluster, including the joining (J) and diversity (D) loci and encompassing approximately 300 kilobases. The relative concentrations of EcoRI segments in bromouracil-labeled DNA that replicated during selected intervals of the S phase in Friend virus-transformed murine erythroleukemia (MEL) cells were measured. From these results, we calculated the nuclear DNA content (C value; the haploid DNA content of a cell in the G1 phase of the cell cycle) at the time each segment replicated during the S phase. We observed that IgCH genes replicate in the following order: alpha, epsilon, gamma 2a, gamma 2b, gamma 1, gamma 3, delta, and mu, followed by the J and D segments. The C value at which each segment replicates increased as a linear function of its distance from C alpha. The average rate of DNA replication in the IgCH gene cluster was determined from these data to be 1.7 to 1.9 kilobases/min, similar to the rate measured for mammalian replicons by autoradiography and electron microscopy (for a review, see H. J. Edenberg and J. A. Huberman, Annu. Rev. Genet. 9:245-284, 1975, and R. G. Martin, Adv. Cancer Res. 34:1-55, 1981). Similar results were obtained with other murine non-B cell lines, including a fibroblast cell line (L60T) and a hepatoma cell line (Hepa 1.6). In contrast, we observed that IgCh segments in a B-cell plasmacytoma (MPC11) and two Abelson murine leukemia virus-transformed pre-B cell lines (22D6 and 300-19O) replicated as early as (300-19P) or earlier than (MPC11 and 22D6) C alpha in MEL cells. Unlike MEL cells, however, all of the IgCH segments in a given B cell line replicated at very similar times during the S phase, so that a temporal directionality in the replication of the IgCH gene cluster was not apparent from these data. These results provide evidence that in murine non-B cells the IgCH, J, and D loci are part of a single replicon.

Abelson murine leukemia virus↗