Biomedical subjects
Publications and source records attributed to S Kakati.
Elephantiasis Nostras Verrucosa (ENV) is a rare form of pretibial myxedema, which is nearly always associated with Graves' disease. A case is presented here of Graves' disease who had elephantiasis variety of pre-tibial myxedema (PTM).
Sudden onset symmetric peripheral gangrene (SPG) is a relatively uncommon clinical entity manifested by distal ischemic damage at two or more sites in the absence of large vessel obstruction. Here we report a case of complicated falciparum malaria with rapid onset SPG involving all the toes.
Cell lines are valuable resources for the study of the malignancy and potential therapy of human breast cancer. A major problem with adapting fresh breast tumor specimens to grow in vitro is contamination by fibroblasts. Previously, we have reported a technique to overcome this problem (Nayak, S. K; Dillman, R. O. Clin. Biotechnol. 3:237-242; 1991). We have recently established two new breast cancer cell lines, HH315 and HH375, that were derived from abdominal and supraclavicular lymph node metastases from two patients. They were characterized by (1) growth kinetics; (2) staining with monoclonal antibodies (MoAbs) to cytokeratin-19, epithelial membrane antigen (EMA), anticarcinoembryonic antigen (CEA), breast cancer antigen 1 (BRST-1), breast cancer antigen 2 (BRST-2), Her2/neu, and p53; (3) expression of domains of urinary plasminogen activator (uPA), neural cell adhesion molecule (NCAM), and haptoglobin (Hp) (Harvey et al., 1997); and (4) karyotypic analysis. Growth kinetic studies showed that doubling times for both lines ranged from 48 to 96 h. These two cell lines were found to have characteristics of the metastatic breast cancer cells. Both lines stained positive with MoAbs to cytokeratin-19 and EMA, thus confirming their epithelial origin. They also strongly reacted with the pan-breast carcinoma MoAbs BRST-1 and BRST-2, and carcinoembryonic CEA MoAb. Both cell lines overexpressed the oncogene proteins Her2/neu and p53. The tumor cells were negative for estrogen and progesterone receptors. HH315 cells were poorly differentiated, whereas the HH375 cells exhibited adenocarcinoma morphology. Both cell lines showed intense cell surface and some cytoplasmic staining for uPA, NCAM, and Hp domains, which is a characteristic of malignant neoplasms (Harvey et al., 1997). The HH375 cell line showed two cell types, of which 60% were hyperdiploids with 60-70 chromosomes and 5-10 marker chromosomes. The remaining cells were polyploid with more than 200 chromosomes. Cell line HH315 consisted of only a polyploid population. These cell lines may be useful in breast cancer research.
Segmental jumping translocations are chromosomal abnormalities in treatment-related leukemias characterized by multiple copies of the ABL and/or MLL oncogenes dispersed throughout the genome and extrachromosomally. Because gene amplification potential accompanies loss of wild-type p53, we examined the p53 gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLL segmental jumping translocation. The child was diagnosed with ganglioneuroma and embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of the t-AML showed structural and numerical abnormalities. Fluorescence in situ hybridization analysis showed multiple copies of the MLL gene, consistent with segmental jumping translocation. A genomic region including CD3, MLL, and a segment of band 11q24 was unrearranged and amplified by Southern blot analysis. There was no family history of a cancer predisposing syndrome, but single-strand conformation polymorphism (SSCP) analysis detected identical band shifts in the leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML. Sequencing showed a CGA-->TGA nonsense mutation at codon 306 in exon 8. The results of this analysis indicate that loss of wild-type p53 may be associated with genomic instability after DNA-damaging chemotherapy and radiation, manifest as a complex karyotype and gene amplification in some cases of t-AML.
The inv(14)(q11q32) is a non-random chromosomal aberration which has been associated with a variety of T-cell malignancies. We have studied a case of inv(14)(q11q32) that is unique in several respects. First, the inversion, which is expressed at the mRNA level, occurred in the context of a pre-B acute lymphoblastic leukemia (ALL) as opposed to a T-cell malignancy. Second, cloning and sequencing of the inversion revealed that it resulted from a fusion between an immunoglobulin heavy chain variable (V) segment and a T-cell receptor delta diversity (D) segment. In addition, the patient had a second chromosomal abnormality at diagnosis, a t(4;11)(q21;q23) which disrupted the MLL gene. The fact that there were two distinct chromosomal abnormalities at diagnosis enabled us to address the question of leukemic clonal evolution during the course of this patient's disease. We present evidence suggesting that the t(4;11)(q21;q23) occurred first, with the inv(14)(q11q32) occurring as a second event.
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Burkitt's lymphoma is quite rare outside of Africa. It is even more uncommon for this nonendemic form of the disease to present in the head and neck region. To our knowledge, nonendemic Burkitt's lymphoma has not been previously reported arising from the parapharyngeal space. We review the case of a 10-year-old boy who presented with an asymptomatic mass at the angle of the mandible several weeks after blunt trauma to that area. We discuss the evaluation of this mass, including the results of computed tomography and magnetic resonance imaging, along with the findings of histopathologic and cytogenetic studies. We also discuss the differential diagnosis of parapharyngeal lesions, paying particular attention to the workup and management of Burkitt's lymphoma. Since Burkitt's lymphoma has the highest growth rate of any tumor in man, rapid diagnosis and immediate treatment are important and likely to improve outcome.
We describe a patient with acute myeloid leukemia (AML) who had a deletion of chromosome 22 at q11 as a sole chromosomal abnormality, resulting in the karyotype 46,XY,del(22)(q11). Southern blot analysis showed no bcr rearrangement and fluorescence in situ hybridization indicated no juxtaposition of c-abl. This study indicates that molecular events other than bcr rearrangement and c-abl juxtaposition were involved in leukemogenesis in this patient. We hypothesize that a tumor suppressor candidate gene may be located on the long arm of chromosome 22; its loss may lead to malignant transformation.
Fifty patients suffering from acute malaria were treated with 'Halofantrine Hydrochloride'. They were observed for 4 weeks. Clinical, haematological and biochemical parameters were assessed for evaluation of halofantrine in acute malaria, with special reference to its effectiveness, tolerability and side effects.
A case of Ramsay Hunt Syndrome with characteristic vesicles on the lateral aspect of the left pinna, evidence of infranuclear palsy of the left 7th cranial nerve, associated with same sided loss of taste sensation in the presulcal area of the tongue and perceptive deafness without vestibular disturbances is reported here. The patient had evidence of aseptic meningitis.
We report the presence of an extra chromosomal element in a family with Wilms' tumor (WT). This family has three children, two of whom were affected. One son, the proband, had bilateral and one daughter had unilateral WT. The first child, the father, and the mother did not have WT. The son with bilateral WT had a ring chromosome (R) both in the lymphocytes as well as in the kidney tissue. The size of the ring varied considerably from cell to cell. The daughter with unilateral WT had an abnormal clone containing a small chromosomal ring (r) in phytohemagglutinin (PHA)-stimulated and Epstein-Barr virus (EBV)-transformed lymphocytes. The mother had a karyotype similar to that of the daughter with WT. We hypothesize that the proband's ring chromosome could be the amplified form of the r inherited from the mother. Chromosome 11 was cytogenetically normal in all the cells examined of the affected children and the unaffected mother. In situ hybridization with a centromere-specific DNA cocktail indicated dispersed centromeric DNA both in r and R.
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Cultured leukocytes of peripheral blood obtained from normal, healthy individuals and from patients with familial polyposis coli (FP) were exposed to 0 rads or 300 rads of 137Cs gamma radiation at G0 to compare damage in these two groups. Only cells in the first mitotic division were considered. The average chromosomal damage in the FP patients was not significantly higher than that in the normal group. The induced chromosomal damage at G0 was normally distributed in both the control and the patient groups as well as when they were combined.
A poorly differentiated sarcoma in a 32-year-old female revealed a large, abnormally banded region in one chromosome #8 in all metaphases. The modal karyotype was 46,XX, -8, +mar. Southern blot hybridization was performed with probes for two protooncogenes located in chromosome 8q (c-MYC and c-MOS). No amplification or rearrangement was observed to account for the cytogenetic abnormality.
Cytogenetic analysis of a primary adrenocortical carcinoma revealed clonal rearrangements of several autosomes and sex chromosomes. In all metaphases the following marker chromosomes were present: 4p+,t(3;12)(p14;p13),14q+, t(15;20)(p11;q11), t(5;18) (p13.3;p11.2), psu dic(18)t(18.3)(p11.39;p12), and psu dic(20)t(20;9)(q11.2;p11). The results are discussed in relation to the cytogenetic findings in other solid tumors, especially of the kidney.
Chromosome analysis of blood cells from a 42-year-old white male with mental retardation, colon carcinoma, horseshoe kidney, absence of left lobe of the liver, agenesis of the gallbladder, and possible Gardner syndrome revealed a constitutional marker chromosome due to del(5)(q13q15) or del(5)(q15q22). A polymorphic chromosome #22 with enlarged satellites was inherited from the father, who is phenotypically normal, and was probably unrelated to the congenital malformations. This is the first report of a Gardner syndrome patient with an interstitial deletion of 5q.
A method is described to generate microcells from human lymphoblasts for use in microcell-mediated chromosome transfer (MMCT). Micronuclei were induced in cells from a human lymphoblastic cell line by prolonged colcemid treatment, and were separated from these lymphoblasts by: attaching the cells to Concanavalin A coated plastic slides designed for enucleation, and centrifuging the slides in medium containing cytochalasin B. Microcells of less than 3 microns in diameter were fused with thymidine kinase negative mouse fibroblasts (LMTK-). HAT medium (hypoxanthine, aminopterin, and thymidine) was used to select microcell hybrids expressing thymidine kinase activity. Positive clones were isolated and Q-banded for chromosome analysis. Unlike previous methods, this procedure permits microcells to be easily generated from lymphoid cells. The methodology of enucleation of microcells may be extended to a variety of other donor cell types which can be micronucleated but which do not adhere tightly to enucleation slides and do not exhibit extrusion subdivision. This feature makes our methodology particularly useful for constructing a library of hybrid clones containing one or a few human chromosomes.
Using dicentric chromosomes and acentric fragments as indicators of radiation sensitivity, a study has been performed on human lymphocyte chromosomes by irradiating peripheral blood cells at G0. Donor-to-donor variation has been noticed regarding radiation sensitivity even when metaphase spreads were scored at the first cell cycle. Thus, it appears that, at the present state, use of chromosomal damage in peripheral blood cell cultures as an effective biological dosimeter for effects of radiation is questionable.