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S L Hasegawa

Publications and source records attributed to S L Hasegawa.

10 recordsLinked to original sources
PubMed2002

Tetrasomy 15q25.3 --> qter resulting from an analphoid supernumerary marker chromosome in a patient with multiple anomalies and bilateral Wilms tumors.

We describe a girl who had been followed since birth for apparent Shprintzen-Goldberg syndrome (SGS), with macrosomia, long fingers and toes, and craniosynostosis, and presented at 4 years of age with bilateral Wilms tumors (also called nephroblastoma). Cytogenetic analysis of her peripheral blood revealed a de novo supernumerary marker chromosome. This stable marker chromosome is present in 19 of 20 lymphocytes analyzed, as well as in all 40 tumor cells (20 from each tumor) studied. Classical and molecular cytogenetic studies indicate that the marker is derived from an inverted duplication of chromosome 15q25.3 --> qter and contains a neocentromere. The presence of this marker chromosome in our patient results in tetrasomy 15q25.3 --> qter. The relationship between her genotype and phenotype are discussed in light of genes, including IGF1R and FES, mapped to the aneusomic segment.

Abnormalities, Multiple↗
PubMed1998

Primary cutaneous Ewing's sarcoma: immunophenotypic and molecular cytogenetic evaluation of five cases.

Cutaneous small blue cell tumors are relatively uncommon and include primary lesions of either adnexal or neuroendocrine differentiation, as well as metastatic disease. Extraosseous Ewing's sarcoma/malignant primitive neuroectodermal tumor (MPNET) rarely may occur as a primary, superficially based neoplasm in children and young adults. We describe a series of five cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor occurring as a primary cutaneous malignancy supported diagnostically both by immunohistochemical stains and fluorescence in situ hybridization (FISH). All five cases occurred as a solitary dermal nodule and were located in the lower extremities (3 cases), the axilla (1 case), and the flank (1 case). Three of the cases were clinically polypoid. Four of the five patients were female, and age at presentation ranged form 8 to 50 years of age (median, 18 years). All five tumors consisted of nodular proliferations of monomorphous, small blue cells with round, vesicular nuclei, and scant to moderate cytoplasm that were uniformly immunoreactive for the CD99 cell surface glycoprotein in a characteristic membranous pattern. Fluorescence in situ hybridization analysis of paraffin-embedded tissue revealed that three of four tumors were positive for a chromosomal translocation involving the EWS locus at 22q12, seen in more than 90% of cases of Ewing's sarcoma/malignant primitive neuroectodermal tumor. One case was not analyzable. All five patients were treated using local excision, and two patients additionally received postoperative chemotherapy and radiotherapy. Clinical follow-up is available in three cases (median duration, 33 months) and to date none has shown evidence of either local recurrence or metastasis. Because similar cases reported in the literature have likewise had favorable clinical courses after excision, primary cutaneous Ewing's sarcoma/malignant primitive neuroectodermal tumor may represent a clinically favorable subset of this otherwise highly aggressive neoplasm.

Adolescent↗
PubMed1997

Schwannomas of the sinonasal tract and nasopharynx.

Approximately 45% of benign peripheral nerve sheath tumors occur in the head and neck region. Of these, schwannomas (neurilemomas) arising from the nasal cavity and paranasal sinuses account for less than 4%. Pathologic features of this subset are not well documented. We report a series of five cases of sinonasal schwannoma and one in the nasopharynx. The male-to-female ratio was equal, and the age at presentation ranged from 38 to 65 years of age (median, 52 yr). Four of the lesions were located within the nasal cavity, one arose from the maxillary sinus, and one originated in the nasopharynx, with extension into the Eustachian tube. Two cases showed local bony destruction, with intracranial extension. Presenting clinical symptoms included nasal obstruction, epistaxis, rhinorrhea, anosmia, facial swelling, headache, and serous otitis media; the two cases with intracranial spread also presented with visual disturbances. All of the six cases were treated by surgical excision. Clinical follow-up in five cases ranged from 6 to 48 months (median, 27 mo). Histologically, all of the lesions shared many cytomorphologic features common to schwannomas arising at other sites, and all of the six cases showed strong, diffuse immunoreactivity for S-100 protein. Four cases showed features of the cellular variant, and one showed focal granular cell change. An unusual and previously poorly documented histologic feature, distinct from schwannomas arising at most other anatomic sites, was a lack of encapsulation, which, when combined with hypercellularity, often raised suspicion of malignancy. Because none of the cases in this series has shown either local recurrence or postoperative metastasis to date, lack of encapsulation and locally destructive growth in an otherwise histologically typical schwannoma arising at this site should not suggest malignant potential.

Adult↗
PubMed1993

Protease treatment of nuclear extracts distinguishes between class II MHC X1 box DNA-binding proteins in wild-type and class II-deficient B cells.

The X box region is critical for directing the expression of class II major histocompatibility complex genes in B lymphocytes. Although several class II promoter-specific DNA binding factors have been described, only the X box region factor, RFX, shows a genetic correlation with class II expression, being deficient in some B cell lines derived from patients with class II-deficient congenital immunodeficiency. To further evaluate the role of X box DNA-binding proteins in class II gene expression, the role of the X box region was examined in both class II-positive and -negative lymphoid cells. In addition to the wild-type B cell line Raji, two class II transcriptional mutant cell lines, SJO and RJ2.2.5, and Jurkat, a class II negative T cell line, were examined. In contrast to wild-type B cells, neither of the class II mutant cell lines could use the X box region to direct the expression of a transiently transfected reporter gene, indicating that the X box-dependent transcriptional pathway is defective in these cells. The binding activity of the X1 box DNA-binding protein RFX was examined and found to be present in wild-type B cells and the mutant RJ2.2.5 but was absent in SJO and Jurkat. However, other X1 box-specific activities were detected in all these cell lines. To determine whether these different X1 box activities represented distinct DNA binding proteins or multimeric forms of the same factor(s), protease treatment of the crude nuclear extracts followed by DNA-binding assays were carried out and demonstrated that B cell extracts contain at least two X1-specific factors. One of these cleaved products (band 1 pk) correlates with RFX activity. A similar comparison with protease-treated extracts prepared from Jurkat cells demonstrated the presence of the band 1pk activity despite an absence of the native RFX activity. In contrast, protease treatment and analysis of SJO extracts showed no detectable levels of the band 1pk activity. These results demonstrate that multiple X1 box-specific DNA-binding activities exist in all lymphoid cells, but the presence of an actively binding RFX species correlates with class II transcription.

B-Lymphocytes↗
PubMed1992

Single base pair substitutions within the HLA-DRA gene promoter separate the functions of the X1 and X2 boxes.

The class II MHC genes are expressed on the surfaces of B cells, activated T cells, and macrophages and may be induced in other cell types by IFN-gamma. The control of class II gene expression has been shown to be mediated by a series of conserved cis-acting sequences (W, X1, X2, and Y boxes) located immediately 5' to the genes. Although these sequences are conserved, the bp that are important for transcriptional regulation have yet to be identified. To address this issue with regard to the MHC gene HLA-DRA, a series of single bp substitutions spanning the conserved upstream sequences was created and analyzed for their effects on transcription in both B cells and IFN-gamma-treated fibroblasts. In addition, the effects of X1 and X2 box mutations on DNA/protein interactions were examined and compared to the transcriptional data. The results of these studies show that each of the conserved elements participate in maximal expression in B cells and that W, X1, and X2 boxes are important for IFN-gamma induction and expression in fibroblasts. Interestingly, some of the bp changes that altered B cell expression did not alter expression and IFN-gamma induction in fibroblasts, suggesting that different or altered factors control the expression of these genes in the different cell types. Mutant templates designed to eliminate the binding of X1- and X2-specific DNA binding proteins in vivo suggest that these elements and their factors may interact to promote transcription.

B-Lymphocytes↗
PubMed1991

Two B cell factors bind the HLA-DRA X box region and recognize different subsets of HLA class II promoters.

The class II genes of the human Major Histocompatibility Complex (MHC) encode three isotypes of alpha/beta heterodimeric proteins, HLA-DR, -DQ, and -DP, which are responsible for presenting processed antigens to T helper lymphocytes. These MHC class II genes are expressed in a coordinate manner. The promoter regions of all MHC class II genes share a set of highly conserved elements that mediate different levels of tissue-specific and inducible transcription. One element, the X box, appears to be the major positive element in B cell-specific expression, and nuclear protein binding studies have subdivided this region into the X1 and X2 boxes. Regulatory Factor X (RFX) binds to the X1 box whereas several other factors have been described that bind to the X2 box. In this report, we further characterize the X1 binding protein RFX and show that RFX binds poorly to beta chain gene promoters. In particular, RFX does not bind to the DRB gene, which is expressed at the highest levels of all beta chain genes. In addition, we have identified an X2 box binding activity in human B cell extracts that binds with high affinity to the HLA-DRA promoter. This X2 binding protein, X2BP, binds to a different subset of class II promoters than does RFX. These findings suggest that coordinate regulation of class II expression may involve different combinations or arrangements of transcriptional elements and factors instead of a common set.

Autoradiography↗
PubMed1991

DNA binding properties of YB-1 and dbpA: binding to double-stranded, single-stranded, and abasic site containing DNAs.

A number of eukaryotic DNA binding proteins have been isolated by screening phage expression libraries with DNA probes containing the binding site of the DNA-binding protein. This methodology was employed here to isolate clones of the factor that interacts with the W box element of the human major histocompatibility complex HLA-DQB gene. Surprisingly, several cDNA clones of YB-1, a cDNA clone that was previously isolated with a CCAAT element-containing sequence were found. Independently, the screening of phage expression libraries with depurinated DNA resulted in the isolation of YB-1 and dbpA, a previously isolated cDNA that has homology to YB-1. Additional characterization of YB-1 showed that it bound a wide variety of DNA sequences and suggested that the binding of this protein is promiscuous. Furthermore, we show that both YB-1 and dbpA bind to depurinated DNA better than undamaged DNA and that the extent of specificity of binding is influenced by Mg2+. Due to the lack of sequence specificity and high degree of binding to depurinated DNA, we suggest that these proteins might be involved in chromosome functions such as maintenance of chromatin structure or DNA repair that do not require sequence-specific binding.

Base Sequence↗
PubMed1991

Regulatory factor-X binding to mutant HLA-DRA promoter sequences.

The class II genes of the major histocompatibility complex (MHC) encode a family of cell surface glycoproteins that present processed antigen to the T cell receptor. Class II genes are regulated coordinately, responding to both immunologic and developmental signals. Conserved sequence elements 5' to class II genes have been shown to be important in transcriptional control. One of these sequences, the X box, is a specific target for the binding of the factor RF-X. In the hereditary HLA class II deficiency, a form of primary immunodeficiency, a regulatory defect in expression of class II genes is associated with a defect in the binding of RF-X. To determine the basepairs that are important for this binding interaction, a series of single basepair substitutions spanning the X box motif of the DRA gene was constructed and tested for binding of RF-X by gel electrophoresis mobility shift assays (EMSAs). Several, but not all, of the mutants severely affected binding of RF-X. In addition, the binding of both the natural and the recombinant form of RF-X was affected with the same specificity. A comparison of X box basepair positions important for RF-X binding to DRA with sequences conserved between X boxes of other class II alpha chain genes suggests that high affinity RF-X binding is important for a high level of expression and may explain differences in the levels of class II expression of different class II alpha chains.

Animals↗
PubMedDate not supplied

Hematogones as an internal control in flow cytometric analysis of suspected acute lymphoblastic leukemia.

Hematogones are benign immature B cells that commonly populate the bone marrow of children. Their presence has been noted to interfere with the flow-cytometric analysis of cases of suspected acute lymphoblastic leukemia (ALL) because their immunophenotype (positive for CD19, CD10, CD34, and terminal deoxynucleotidyl transferase) is similar to that of pre-B cell lymphoblasts. Here we report a case in which the presence of a discrete population of hematogones, characterized by low-intensity CD10 cell-surface staining compared with pre-B cell lymphoblasts, actually aided in the recognition of early relapsed ALL and disease progression over a 4-day period. We also review our experience with flow-cytometric immunophenotyping in pediatric cases of suspected leukemia to evaluate the frequency of this occurrence.

Antigens, CD19↗