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A S Multani

Publications and source records attributed to A S Multani.

At least 37 records · Page 2Linked to original sources
PubMed1998

Amplification of telomeric DNA and the extent of karyotypic evolution.

The distribution of telomeric DNA in the genomes of the antelope ground squirrel, Ammospermophilus harrisii (family Sciuridae; 2n = 32) and the African black-footed cat, Felis nigripes (family Felidae; 2n = 38) were compared by fluorescence in situ hybridization (FISH) technique. These two mammalian species have the highest and the lowest amount of C-banded regions, respectively. FISH preparations with the human telomeric DNA probe showed that all C-banded segments in the A. harrisii chromosomes, except a few intercalary segments, were hybridizing with this DNA. F. nigripes showed hybridization only on the termini of each chromosome, and the C-banded regions did not hybridize with telomeric DNA on FISH analysis. The C-banded chromosomal arms in another rodent species, Peromyscus eremicus (family Cricetidae; 2n = 48), when hybridized with human telomeric DNA showed signals only in the termini of chromosomes but not in the heterochromatic arms. These observations indicate that not all C-banded regions in rodent species are telomeric DNA. The amplification of telomeric DNA in relation to speciation is discussed.

Animals↗
PubMed1997

Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial.

Human colonic cancer is associated with multiple genetic deletions, mutations, and alterations in gene expression; in contrast, gene amplification has not been recognized as a prominent characteristic of human colonic tumors. Although the c-myc gene is overexpressed in approximately 70% of human colonic cancers, previous studies have not detected frequent gene amplification or rearrangement of c-myc in these tumors, although such amplification has been reported in chemically induced rodent colon cancer and quantitative analysis of gene copy number has shown the gene to be amplified at a low level in mucinous and poorly differentiated human colon carcinomas. Using rigorously controlled blot methodology, we have established that the c-myc gene, located at 8q21, exhibited amplification of 87% to 35-fold in 7 of 10 human colonic carcinoma cell lines. This was highly significant even at a low level of amplification in HT29 cells (P < 0.0001). Cytogenetic analysis by G-banding did not detect aneuploidy involving chromsome 8q, suggesting that the amplification for the c-myc gene on 8q was relatively specific, and this was consistent with a lack of amplification detected for the c-mos gene on 8q24, which was assayed similarly. The same methodology then revealed amplification of c-myc from 1.5-fold to 5-fold in 32% of tumors from 149 patients entered into a multi-institutional Phase III study of adjuvant therapy for colon cancer. c-myc status was not related to time to recurrence or death, but low levels of c-myc amplification identified a subset of patients who showed a statistically significant increase in disease-free survival, and a corresponding trend to longer overall survival, in response to adjuvant therapy with 5-fluorouracil plus levamisole. Presence of c-myc amplification was not related to incidence of p53 mutations.

Carcinoma↗
PubMed1997

Can cancer cells transform normal host cells into malignant cells?

A human prostate tumour cell line, LNCaP C4-2, when injected into athymic male nude mice, produced tumours containing: (1) only human cancer cells similar to those injected; (2) only murine stromal cells containing abnormal chromosome constitutions; or (3) both human prostate cancer cells similar to those injected and the transformed murine stromal cells with altered chromosome constitutions. Karyotypic analysis of murine metaphases from all the host-derived tumours showed mostly pseudodiploid chromosome constitutions, with multiple copies (amplification) of mouse chromosome 15 and the absence of a typical Y chromosome. Fluorescence in situ hybridization analysis of these murine cells, using a biotin-labelled total human DNA painting probe, further demonstrated the absence of human DNA and the presence of only mouse metaphase and interphase cells in these transformed stromal cells. These results suggest that cancer cells are capable of inducing neoplastic transformation in stromal cells of the host organ by some, as yet unknown, epigenetic mechanism(s).

Animals↗
PubMed1997

Reflux oesophagitis in acid peptic disease (a fibre-optic endoscopic study).

This study is based on entry criteria of visual findings of the upper gastro-intestinal fibre-optic endoscopy performed on 100 patients suffering from acid peptic disease (dyspepsia). The diagnostic criteria and grading of reflux oesophagitis advocated by Savary and Miller have been adopted. Reflux oesophagitis was found in 43 cases having grade I oesophagitis in 48.84%, grade II in 32.56%, grade III in 14.00% and grade IV in 4.60% cases. Reflux oesophagitis was associated with hiatus hernia in 23.26%, chronic gastritis in 9.30% of cases. The age varied from 16-80 years with almost equal incidence of male and female, and the severity of the disease increased with the advancement of age. Endoscopy is advised in every case of dyspepsia before any treatment is initiated.

Adolescent↗
PubMed1997

Specific histologic and cytogenetic evidence for in vivo malignant transformation of murine host cells by three human prostate cancer cell lines.

The chromosomal constitutions of three murine cell lines that developed in vitro from tumors that grew in nude mice after orthotopic and ectopic injections of three human prostate tumor cell lines were examined by histopathology, conventional G-banding, and with fluorescence in situ hybridization techniques. All three murine cell lines showed unique marker chromosomes involving mouse chromosome 12, with a common break point. Histopathologic evidence from a murine prostate gland into which SP 3031 cells had been injected indicated dysplastic glandular epithelium and carcinomatous areas. These observations further indicate that: (a) human prostate tumors are capable of transforming host organ cells, (b) host cells have specific chromosomal alterations that may be associated with transformation, and (c) the process of host cell transformation can be demonstrated in histological sections. Although cancer cell heterogeneity and drug-resistant phenotypes are caused by additional genetic alterations and clonal evolution of the original tumor, transformation of the host's distant organ cells may also contribute because most therapies are directed only to the original cancer cells.

Animals↗
PubMed1996

Three siblings with Harlequin Ichthyosis in an Indian family.

The Harlequin fetus is a distinct genetic entity with a strikingly grotesque appearance. Three siblings (two males, one female) with Harlequin Ichthyosis, a rare form of congenital disorder, born to the same parents are presented. The genetic aspects are discussed and the relevant literature is reviewed.

Abnormalities, Multiple↗
PubMed1996

Incomplete gonadal dysgenesis.

A 21-year-old phenotypic male with ambiguous external genitalia and hypospadias was referred for cytogenetic studies. Exploratory laparotomy revealed presence of a small atropic uterus, unilateral gonadal dysgenesis with fallopian tubes on both sides and a cryptorchid testis on the left side. No gonad could be traced on the right side. Chromosomal analysis from peripheral whole blood culture revealed a 46,XY cell line. No mosaicism was detected. Endocrine studies showed elevated levels of serum FSH and LH with low borderline testosterone level and failure to respond to HCG stimulation. The presence of fallopian tube next to testis suggests absence of anti-Mullerian hormone secretion by Sertoli cells. The absence of Wolffian duct derivatives indicates insufficient secretion of testosterone by Leydig cells.

Adult↗
PubMed1993

Polydactyly: a study of a five generation Indian family.

Preaxial polydactyly was observed in up to five generations of an Indian family living in a village in the Rajkot district (Gujarat). Among the 71 affected members, 45 were males and 26 were females. All these affected members showed preaxial polydactyly manifesting as a well formed, articulated extra digit of the hand or foot. Twenty other cases were also identified with polydactyly involving triphalangeal digits replacing the thumbs or duplication of the big toe(s). To the best of our knowledge, the present family is the largest in which several members have preaxial polydactyly of different types. No other abnormalities were apparent. The present study strongly suggests that preaxial polydactyly with a well formed extra digit, triphalangeal thumbs, and duplication of the big toe can be manifestations of the same autosomal dominant gene. It is likely that other factors are modifying the expression of this gene.

Adult↗
PubMed1992

Translocation t(22;22)(p11.1;q11.1) and NOR studies in a female with a history of repeated fetal loss.

A 32-year-old phenotypic female with a history of nine consecutive abortions each in the first trimester was referred for cytogenetic studies. She was found to have 45,XX,t(22;22) (p11.1;q11.1) chromosomal pattern. The Ag-NOR banding technique showed that the NORs of both the acrocentrics involved in the translocation were deleted and the loss suffered from the elimination was compensated by the increased NOR activity as well as presence of dNOR on other acrocentric chromosomes.

Abortion, Habitual↗
PubMedDate not supplied

Caspase-dependent apoptosis induced by telomere cleavage and TRF2 loss.

Chromosomal abnormalities involving telomeric associations (TAs) often precede replicative senescence and abnormal chromosome configurations. We report here that telomere cleavage following exposure to proapoptotic agents is an early event in apoptosis. Exposure of human and murine cancer cells to a variety of pro-apoptotic stimuli (staurosporine, thapsigargin, anti-Fas antibody, and cancer chemotherapeutic agents) resulted in telomere cleavage and aggregation, and finally their extrusion from the nuclei. Telomere loss was associated with arrest of cells in G2/M phase and preceded DNA fragmentation. Telomere erosion and subsequent large-scale chromatin cleavage were inhibited by overexpression of the anti-apoptotic protein, bcl-2, and two peptide caspase inhibitors (BACMK and zVADfmk), indicating that both events are regulated by caspase activation. The results demonstrate that telomere cleavage is an early chromatin alteration detected in various cancer cell lines leading to drug-induced apoptosis, and suggest that this event contributes to mitotic catastrophe and induction of cell death. Results also suggest that the decrease of telomeric-repeat binding factor 2 (TRF2) may be the earliest event in the ara-C-induced telomere shortening, induction of endoreduplication and chromosomal fragmentation leading to cell death.

Animals↗
PubMedDate not supplied

Dolastatin-10 induces polyploidy, telomeric associations and apoptosis in a murine melanoma cell line.

Our purpose was to study the effects of dolastatin-10 (Dol-10) on chromosome morphology, telomeric associations, induction of polyploidy and cell death in a metastatic murine melanoma cell line, K1735 clone X-21. Murine melanoma cells were treated with various concentrations (10 ng/ml, 100 ng/ml and 1000 ng/ml) of Dol-10 for 4, 24 and 72 h continuously and harvested immediately without recovery. In another set of experiments, cells were treated for 4 h with the same concentrations, washed with prewarmed medium and then allowed to recover in drug-free medium for 24 h and subsequently harvested. Our preliminary results indicated: i) a drug-mediated increase in the frequency of metaphases, with telomeric associations resulting in multicentric and ring configurations; ii) induction of clumping in metaphase chromosomes; iii) induction of polyploidy as a result of endoreduplication; iv) formation of micronucleated cells; and v) induction of cell death. These observations indicated that Dol-10 could be a potent antineoplastic drug against malignant melanoma. In addition to its reported interaction with cell microtubules, the mechanism of action of Dol-10 may be mediated through the loss of telomeric repeats and induction of chromosome aberrations.

Animals↗
PubMedDate not supplied

Cell-killing by paclitaxel in a metastatic murine melanoma cell line is mediated by extensive telomere erosion with no decrease in telomerase activity.

The purpose of this study was to investigate and compare the effects of paclitaxel and its water-soluble conjugates (sodium-pentetic acid-paclitaxel; polyethylene glycol-paclitaxel, and poly[L-glutamic acid]-paclitaxel) on chromosome morphology and induction of apoptosis in a metastatic murine melanoma cell line (K1735 clone X-21). For this, murine melanoma cells were treated continuously for 72 h with three concentrations (1.2 microM, 2.4 microM, and 4.8 microM) of each of paclitaxel, and conjugates. Another set of cells were pulse-treated at 2.4 microM, 4.8 microM and 9.6 microM concentrations of each of these drugs for 4 h and the recovered cells were examined after 72 h. Control cultures received only the solvents (dimethyl sulfoxide or water). Our results showed a significant increase in the frequencies of telomeric associations, chromosome aberrations, polyploidization, distorted and disintegrated chromosome morphology, and reduced telomeric signal intensity by fluorescence in situ hybridization, in treated cultures as compared to the controls. However, we detected no change in telomerase activity. In addition, the majority of interphase nuclei in treated cells showed apoptotic bodies, with chromatin condensation. These in vitro results suggest that cell death induced by paclitaxel and its water-soluble conjugates is due to the loss of telomeric repeats, as shown by reduced signal flourescence and increased telomeric associations.

Animals↗
PubMedDate not supplied

Conventional cytogenetics alone is not sufficient for identifying interspecies cell line contamination.

Evidence from our laboratory suggests that conventional chromosome banding analysis alone is not sufficient for detecting interspecies contamination of cell lines. To differentiate noncycling interphase cells of murine or other species origin that may be contaminating a human cell line, molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH) with a total human DNA probe must be used.

Animal Population Groups↗
PubMedDate not supplied

Non-random primary and secondary chromosomal abnormalities in human gastric cancers.

By using Giemsa-banding and fluorescence in situ hybridization techniques, we have been able to identify primary and secondary cytogenetic abnormalities in four gastric tumors at different stages of development. Structural and numerical abnormalities were present in all four gastric tumors in chromosomes 3, 7, 11, and X. Other abnormalities involving chromosomes 1, 5, 6, 8, 13, 15, 17, 18, 19 and 22 were observed, but only in three advanced gastric tumors, suggesting that these were secondary/tertiary genetic defects. Based on these results it was possible for us to decipher primary and secondary genetic abnormalities in these four gastric tumors.

Biopsy↗
PubMedDate not supplied

A modified fluorescence in situ hybridization (FISH) technique.

We have modified and shortened the routine fluorescence in situ hybridization (FISH) technique by using microwave or formalin pretreatment for artificially aging and microwave heating only for dehydrating the regular chromosome preparations. The all-human telomere probe (Oncor, Inc., Gaithersburg, MD) was used on murine K-1735 clone X-21 melanoma cells for this purpose. The intensity of signals obtained by our modified technique(s) was comparable to that obtained by the routine procedure. However, pretreatment of slides with hydrogen peroxide (H2O2) completely obliterates the FISH signals.

Animals↗