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S Pathak

Publications and source records attributed to S Pathak.

At least 55 records · Page 3Linked to original sources
PubMed1988

An electron microscopical study of the replication of avirulent Semliki Forest virus in the retina of mice.

Electron microscopical (EM) studies were carried out on the retinas of 2-3-(baby), 12-, 14- and 21-28-day-old (adult) mice infected with avirulent (A774) Semliki Forest virus (SFV). Virions (mature virus), spherules and advanced stages of virus replication, cytopathic vacuoles type II (CPV II), were seen in the retinal neurons of baby mice after intracerebral (i.c.) or intraperitoneal (i.p.) infection. Some virions and spherules were also seen in the retinas of 12- and 14-day-old mice. Virions and advanced stages of virus replication were not seen in adult mice despite high virus titres. Some neurons of the inner nuclear layer and some ganglion cells showed reduced basophilia and appeared pale and occasionally some dense clumps of fine granules (DC) were seen in the neurones of the inner nuclear layer in these mice. A few small spherules were seen in the extracellular spaces. Some infiltrating cells were seen in the retinas in all ages of mice. We suggest that SFV causes retinopathy in baby mice and the neurophysiological changes reported in adult mice may be contributed to by virus replication in the retinal neurones and the presence of infiltrating cells in the retina.

Animals↗
PubMed1988

Telomeric association: another characteristic of cancer chromosomes?

Telomeric associations between single chromatids and double chromatids of nonhomologous normal human chromosomes and altered markers were observed in two morphologically distinct squamous-cell carcinoma lines derived from a surgical specimen. Chromosomes 2, 3, 5, and 16 were associated by their telomeric ends more frequently than other chromosomes.

Carcinoma, Squamous Cell↗
PubMed1988

Effect of epidermal growth factor (EGF) on a newly established head and neck squamous carcinoma cell line.

A new cell line designated 584A2 has been recently established from a patient with squamous cell carcinoma of the larynx. Cytogenetic analysis of the cell line revealed multiple copies of chromosome 7, as well as a homogeneous staining region (HSR) on one chromosome 7. Since overexpression of epidermal growth factor (EGF) cell surface receptors (EGFr) often occurs in other squamous carcinoma cell lines, it was predicted that 584A2 might overexpress EFGr. This was confirmed by: (1) metabolic labeling, with subsequent immunoprecipitation of EGFr and comparing autoradiographs to a cell line without an HSR and fewer copies of chromosome 7, and (2) performing EGF binding assays with Scatchard analysis. Since overexpression of EGFr correlates with an inhibitory effect of EGF on cell culture, the biological effects of EGF on 584A2 were examined in this study. At 5 ng/ml (serum-free medium), EFG stimulated incorporation of [3H] thymidine into trichloroacetic acid-precipitable material compared with controls. Incorporation increased between days 0 to 1 and 1 to 2 days with a 6- to 7-fold maximum. Dose-response studies (0 to 100 ng/ml) indicated maximum incorporation (6- to 7-fold) occurred between 0.1 ng/ml and 1.0 ng/ml. Cell growth was monitored over 7 days and, during this time, 5 ng/ml EGF produced a 10- to 12-fold increase in absolute cell numbers when compared with controls. We concluded that, unlike other squamous carcinoma lines with elevated EGFr, EGF stimulates rather than inhibits 584A2 cell proliferation.

Carcinoma, Squamous Cell↗
PubMed1988

Ag-NOR staining in the Bennett wallaby, Macropus rufogriseus: evidence for dosage compensation.

Silver staining of cells in metaphase and interphase nuclei of both sexes of the Bennett wallaby, Macropus rufogriseus, has shown that (1) the nucleolus organizer region (NOR) is located only on the X chromosome (single Ag-NOR); (2) both X chromosomes in the female cells stain with silver; (3) the amounts of silver staining of metaphase chromosomes and interphase nuclei of both sexes are very similar; (4) the single X chromosome is hyperactive in male cells to equalize the expression of rRNA genes in the female cells with two X chromosomes; and (5) the mechanism of dosage compensation for rRNA genes in this species is similar to that reported for Drosophila salivary gland cells.

Anaphase↗
PubMed1988

Bcl-1 gene rearrangements in B cell lymphoma.

We analyzed 50 B cell lymphoma samples by Southern blot analysis, using the bcl-1 and heavy chain immunoglobulin (JH) probes with two or more restriction endonucleases. All samples showed JH rearrangement, and three samples (two diffuse small lymphocytic lymphomas and one diffuse large cell lymphoma probably transformed from a diffuse small lymphocytic lymphoma) demonstrated rearranged bcl-1 sequences. The three samples showed the t(11;14)(q13;q32) chromosome translocation, and all three contained rearranged JH fragments that comigrated with the rearranged bcl-1 fragment. The breakpoint of the translocation occurred within a 1.6-kb region on chromosome 11 in the three cases. Two of the three patients had primary refractory disease. Two of the three patients had gastrointestinal involvement. Bcl-1 rearrangement may identify an unusual subset of patients with primary refractory disease with gastrointestinal involvement. It may also describe a unique subset of large cell lymphoma patients transformed from diffuse small cell histology.

B-Lymphocytes↗
PubMed1988

Plasma cell karyotype in multiple myeloma.

Karyotypic abnormalities were studied in multiple myeloma and were correlated with clinical features. Among 115 evaluable patients, 46% had an abnormal karyotype. Trisomy 3, 5, 9, and 15 and monosomy 13 and 16 were the most common clonal abnormalities. Translocations described previously in other B cell malignancies occurred in nine patients, including four with t(8;14)(q24;q32) translocations. The association of all t(8;14) abnormalities with IgA protein type suggested a pathogenetic relationship between a specific karyotypic abnormality and myeloma protein type. Hypodiploidy occurred mainly in patients with only Bence Jones protein, was associated with resistance to therapy, and justified the early consideration of investigational therapies.

Chromosome Aberrations↗
PubMed1988

Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte.

Surface marker and gene rearrangement data have supported various hypotheses about the origin of the malignant cell in Hodgkin's disease. Cytogenetic data about this disorder, however, are very scanty. To determine if any chromosomal abnormalities that could add further information to this controversial point are present, we studied tumor samples from 49 patients. Abnormal metaphases were obtained in 18 cases. The most common breakpoints were in 11q23, 14q32, 6q11-21, and 8q22-24. These are common breakpoints in lymphoma and raise the possibility that the malignant cell in Hodgkin's disease may be derived from a lymphocyte. The 11q23 breakpoint is also seen in t(4;11) and t(9;11), which is typical of a type of childhood B-cell acute lymphoblastic leukemia characterized by the presence of aberrant myeloid and monocytic markers. Myeloid and monocytic markers are common in Reed-Sternberg cells.

Chromosome Aberrations↗
PubMed1987

Involvement of chromosome 7 in primary lung tumor and nonmalignant normal lung tissue.

By using the newly developed adhesive tumor cell culture system, we analyzed the chromosomal constitutions of primary lung tumor and nonmalignant normal lung tissue from 10 previously untreated patients with non-small cell lung cancer. Chromosomal analyses were successfully carried out in banded chromosome preparations from 10 tumor and 8 normal lung tissue samples. All analyzed tumor and normal lung tissue samples had a predominantly normal diploid chromosome number. However, there was at least one structural or numerical alteration in every tumor and lung tissue sample analyzed. Chromosomes 1, 3, 4, 6, 7, 8, 9, 12, 15, and 20 were more often involved in rearrangement. The most consistent finding was trisomy 7; 4 patients had trisomy 7 in both tumor and normal lung tissue, and another 2 had this anomaly in tumor tissue only. Of the 4 patients without trisomy 7, 2 had a homogeneously staining region in the short arm of chromosome 7 in tumor tissue. Phytohemagglutinin-stimulated peripheral blood lymphocytes from 7 patients, including 5 patients with trisomy 7 in tumor tissue, did not show trisomy 7. These cytogenetic data suggest that chromosome 7 may be associated with lung cancer development and that trisomy 7 may be the hallmark of premalignant changes, at least in a subgroup of patients with non-small cell lung cancer.

Aged↗
PubMed1987

Selection of metastatic variants with identifiable karyotypic changes from a nonmetastatic murine tumor after treatment with 2'-deoxy-5-azacytidine or hydroxyurea: implications for the mechanisms of tumor progression.

Experiments were undertaken to explore whether in vitro exposure of a nonmetastatic murine tumor to chemotherapeutic drugs would affect the ability of this tumor to metastasize spontaneously. The tumor chosen was an aneuploid (near-tetraploid) spontaneously arising intraductal mammary adenocarcinoma (CBA-SP1), which normally fails to give rise to microscopic or macroscopic metastases after s.c. inoculation of cells. The drugs tested were 5-aza-2'-deoxycytidine (5-aza-dCyd) and hydroxyurea. We found that the injection of 1 X 10(5) uncloned drug-treated cells s.c. resulted in the emergence of gross and/or microscopically detectable metastases in the lungs of CBA mice. Individual clones derived from hydroxyurea-treated cells all produced metastases in a manner similar to the bulk culture injections. Clones of 5-aza-dCyd-treated cells also produced metastases, but fewer of these produced macroscopic metastases. In addition, only 9 of 15 5-aza-dCyd-treated clones produced tumor takes because of the ability of 5-Aza-dCyd to engender Imm+ variants in CBA-SP1 cells. Lung metastases obtained after the injection of uncloned cells retained their metastatic phenotype for three generations, indicating that the phenotypic change was a heritable characteristic. Although the genetic or epigenetic mechanism for this change is unknown, we observed karyotypic changes of a similar nature in the drug-treated cell lines established from micrometastases. These involved the detection of extra copies of chromosome 8. It is possible that exposure of tumors to therapeutic agents may in some cases increase their aggressiveness through genetic or epigenetic mechanisms that lead to high frequency heritable phenotypic alterations associated with distinguishable chromosomal changes.

Animals↗
PubMed1987

Genetic instability in fibroblasts of patients with thyroid cancers (TC).

In cultured fibroblasts initiated from fresh tumor biopsies of 11 patients with thyroid tumors, 5 medullary carcinoma of the thyroid (MCT) and 6 papillary follicular, the chromosomes are relatively unstable when compared with those from control fibroblast cultures. Tumor-derived fibroblast samples showed a mean number of cells in metaphase with chromosome abnormalities at a frequency of 9.1% and a range of 6-13%, whereas 5 controls exhibited a mean frequency of 4% and a range of 3-5%. Our results indicate that genetic instability in thyroid cancer patients is present not only in peripheral blood cultures, as reported earlier, but in their fibroblast cultures as well.

Cells, Cultured↗
PubMed1987

Variation in the expression of aphidicolin-induced fragile sites in human lymphocyte cultures.

A correlation between specific fragile sites and cancer breakpoints has been suggested raising the question of fragile site expression as a predisposing factor in the occurrence of cancer in some persons. Before addressing the question of increased fragility among patients at high risk for cancer, we analyzed the variability of aphidicolin-induced fragile sites among nine normal persons and also among repeated samples from three of these individuals. Considerable variation in both the frequency and location of these fragile sites was observed and the data strongly suggest the significant variation of 6 of the 16 selected sites to be primarily due to sampling differences. These findings indicate that the use of fragile sites as a screening tool for patients at high risk of cancer should be carefully monitored relative to the variation inherent in both culture and individual expression.

Aphidicolin↗
PubMed1987

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗
PubMed1987

Ph-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line with similar cytogenetic pattern.

Blast cells from a 39-year-old man in the blastic phase of chronic myeloid leukemia, with a benign phase of 15 years duration, as well as a cell line arising from this cell population, were studied. Cellular morphology, cytochemical staining pattern, and absence of terminal deoxynucleotidyl transferase showed the blast cells to be of myeloid character. Cytogenetic studies revealed the presence of two near-haploid cell populations with +8 and +8, +15, respectively, both of them containing the translocation t(9;22) in the original tumor cell sample. The cell line derived from this patient's leukemic cell sample contained both near-haploid and hyperdiploid clones, the hyperdiploid clones being multiples of the near-haploid clone(s). All of the clones carried the t(9;22) in the form of a Philadelphia chromosome.

Adult↗
PubMed1987

Nonrandom loss of maternal chromosome 11 alleles in Wilms tumors.

A series of gene probes for chromosome 11 has been used to study the genetic events associated with the development of Wilms tumor. Examination of DNA samples from five patients with Wilms tumor in whom the tumors showed loss of chromosome 11 alleles and their parents indicate that alleles lost in the tumors are of maternal origin. These data suggest that the parental derivation of chromosome 11 alleles lost in these Wilms tumors is not random.

Alleles↗
PubMed1987

Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor.

Wilms tumor, a common childhood renal tumor, occurs in both a heritable and a nonheritable form. The heritable form may occasionally be attributed to a chromosome deletion at 11p13, and tumors from patients with normal constitutional chromosomes often show deletion or rearrangement of 11p13. It has been suggested that a germinal or somatic mutation may occur on one chromosome 11 and predispose to Wilms tumor and that a subsequent somatic genetic event on the normal homologue at 11p13 may permit tumor development. To study the frequency and mechanism of such tumor-specific genetic events, we have examined the karyotype and chromosome 11 genotype of normal and tumor tissues from 13 childhood renal tumor patients with different histologic tumor types and associated clinical conditions. Tumors of eight of the 12 Wilms tumor patients, including all viable tumors examined directly, show molecular evidence of loss of 11p DNA sequences by somatic recombination (four cases), chromosome loss (two cases), and recombination (two cases) or chromosome loss and duplication. One malignant rhabdoid tumor in a patient heterozygous for multiple 11p markers did not show any tumor-specific 11p alteration. These findings confirm the critical role of 11p sequences in Wilms tumor development and reveal that mitotic recombination may be the most frequent mechanism by which tumors develop.

Child↗
PubMed1987

The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas.

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).

Bone Marrow Cells↗
PubMed1987

Cytogenetic analysis of a gossypol-induced murine myxosarcoma.

Cytogenetic analysis of gossypol acetate-induced murine myxosarcoma demonstrated a stemline of 78 chromosomes and the presence of three marker (M) chromosomes produced by robertsonian translocation. Tumor cells at passage 1 that contain chromosomes M1 and M2 were nontumorigenic, whereas cells at passage 3 were tumorigenic in syngeneic mice and showed M1, M2, and M3. The presence of M3 has been implicated to be responsible for the tumorigenic phenotype.

Animals↗