Variations in radiographic appearance of articular cartilage of knee joints in persons of 35 to 65 years of age

Background:Osteoarthritis is a slowly progressive degenerative disease characterized by gradual loss of articular cartilage. Osteoarthritis is not a normal process of ageing processes. Age related changes are distinct from osteoarthritic changes but when coupled with certain precipitating factors like obesity, muscle weakness and neurological dysfunction may play an important role in the causation of osteoarthritis. Osteoarthritis occurrence appears to increase with patient’s age in a non-linear fashion. The prevalence of disease increases dramatically after the age of 50 years, likely because of age related alterations in collagen and proteoglycan synthesis coupled with diminished nutrient supply to the cartilage.Methods:In this paper presenting the naked eye assessment of radiographic appearance of articular cartilage of knee joints of 100 persons (both men and women) of 35 to 65 years of age with symptoms like pain and stiffness of the joint.Results:Parameters like changes in the joint space width, the presence or absence of osteophytes and subchondral sclerosis and cysts were noted.  The correlation between the patient’s age, sex, symptoms and radiological appearance were observed.Conclusion:Osteoarthritis has a higher prevalence and more often generalized in women than in men. Before the age of 50 years, the incidence of osteoarthritis is low and men have a slightly higher prevalence than women, but after the age of 50 years, the disease becomes more frequent and women have a much higher prevalence with a female to male ration of about 12:1. The reason for this is sex difference in cartilage volume.

Molecular Cytogenetic Applications in Analysis of the Cancer Genome

Cancer cells exhibit nonrandom and complex chromosome abnormalities. The role of genomic changes in cancer is well established. However, the identification of complex and cryptic chromosomal changes is beyond the resolution of conventional banding methods. The fluorescence microscopy afforded by imaging technologies, developed recently, facilitates a precise identification of these chromosome alterations in cancer. The three most commonly utilized molecular cytogenetics methods comparative genomic hybridization, spectral karyotype, and fluorescence in situ hybridization, that have already become benchmark tools in cancer cytogenetics, are described in this chapter. Comparative genomic hybridization is a powerful tool for screening copy-number changes in tumor genomes without the need for preparation of metaphases from tumor cells. Multicolor spectral karyotype permits visualization of all chromosomes in one experiment permitting identification of precise chromosomal changes on metaphases derived from tumor cells. The uses of fluorescence in situ hybridization are diverse, including mapping of alteration in single copy genes, chromosomal regions, or entire chromosomes. The opportunities to detect genetic alterations in cancer cells continue to evolve with the use of these methodologies both in diagnosis and research

Comprehensive Molecular Cytogenetic Characterization of Cervical Cancer Cell Lines

We applied a combination of molecular cytogenetic methods, including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH), to characterize the genetic aberrations in eight widely used cervical cancer (CC) cell lines. CGH identified the most frequent chromosomal losses including 2q, 3p, 4q, 6q, 8p, 9p, 10p, 13q, and 18q; gains including 3q, 5p, 5q, 8q, 9q, 11q, 14q, 16q, 17q, and 20q; and high-level chromosomal amplification at 3q21, 7p11, 8q23– q24, 10q21, 11q13, 16q23– q24, 20q11.2, and 20q13. Several recurrent structural chromosomal rearrangements, including der(5)t(5;8)(p13;q23) and i(5)(p10); deletions affecting chromosome bands 5p11, 5q11, and 11q23; and breakpoint clusters at 2q31, 3p10, 3q25, 5p13, 5q11, 7q11.2, 7q22, 8p11.2, 8q11.2, 10p11.2, 11p11.2, 14q10, 15q10, 18q21, and 22q11.2 were identified by SKY. We detected integration of HPV16 sequences by FISH on the derivative chromosomes involving bands 18p10 and 18p11 in cell line C-4I, 2p16, 5q21, 5q23, 6q, 8q24, 10, 11p11, 15q, and 18p11 in Ca Ski, and normal chromosome 17 at 17p13 in ME-180. FISH analysis was also used further to determine the copy number changes of PIKA3CA and MYC. This comprehensive cytogenetic characterization of eight CC cell lines enhances their utility in experimental studies aimed at gene discovery and functional analysis

A handcuff model for the cohesin complex

The cohesin complex is responsible for the accurate separation of sister chromatids into two daughter cells. Several models for the cohesin complex have been proposed, but the one-ring embrace model currently predominates the field. However, the static configuration of the embrace model is not flexible enough for cohesins to perform their functions during DNA replication, transcription, and DNA repair. We used coimmunoprecipitation, a protein fragment complement assay, and a yeast two-hybrid assay to analyze the protein–protein interactions among cohesin subunits. The results show that three of the four human cohesin core subunits (Smc1, Smc3, and Rad21) interact with themselves in an Scc3 (SA1/SA2)-dependent manner. These data support a two-ring handcuff model for the cohesin complex, which is flexible enough to establish and maintain sister chromatid cohesion as well as ensure the fidelity of chromosome segregation in higher eukaryotes

The t(2;3)(q21;q27) translocation in non-Hodgkin's lymphoma displays BCL6 mutations in the 5' regulatory region and chromosomal breakpoints distant from the gene

The BCL6 gene, mapped at the chromosomal band 3q27, encodes a POZ/Zinc finger transcription repressor protein. It is frequently activated in Non-Hodgkin's lymphomas (NHL) by translocations with breakpoints clustering in the 5' major breakpoint region (MBR) as well as by mutations in the same region. The translocations lead to BCL6 activation by substitution of promoters of rearranging genes derived from the reciprocal chromosomal partners such as IG. We report the molecular genetic analysis of a novel t(2;3)(q21;q27) translocation subset in NHL comprising three cases without apparent BCL6 involvement in the translocation. Southern blot analysis of tumor DNAs utilizing BCL6 MBR probes revealed no rearrangement in two cases. Two rearranged bands in the third case resulted from a deletion in one allele and a mutation in the other allele. Southern blot analysis of DNA from one of the two tumors without BCL6 rearrangement, using a probe derived from the recently identified alternative breakpoint region (ABR), showed a rearrangement. The ABR is located 200-270 kb telomeric to MBR. Mutations were identified in the previously reported hypermutable region of BCL6 in all three tumors. In one, the mutant allele alone was found to be expressed by RT-PCR analysis of RNA. These results demonstrate the presence of 3q27 translocation breakpoints at a distance from BCL6 suggesting distant breaks that deregulate the gene or involvement of other genes that may be subject to rearrangement

Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma

The pathogenesis of multiple myeloma (MM), an incurable tumour causing the deregulated proliferation of terminally differentiated 8 cells, is unknown 1• Chromosomal translocations (14q1) affecting band 14q32 and unidentified partner chromosomes are common in this tumour, suggesting that they may cause the activation of novel oncogenes2.3. By cloning the chromosomal breakpoints in an MM cell line, we show that the 14q+ translocation represents a t(6;14)(p2S;q32) and that this aberration is recurrent in MM, as it was found in two of eleven MM cell lines. The translocation juxtaposes the immunoglobulin heavy-chain (lgH) locus to MUM1 (mM:Itiple myeloma oncogene 1JIIRF4 gene, a member of the interferon regulatory factor (IRF) family known to be active in the control of 8-cell proliferation and differentiation. As a result, the MUM1RRF4 gene is overexpressed-an event that may contribute to tumorigenesis, as MUM11/RF4 has oncogenic activity in vitro. These findings identify a novel genetic alteration associated with MM, with implications for the pathogenesis and diagnostics of this tumour

Chromosomal aberrations in patients with head and neck squamous cell carcinoma do not vary based on severity of tobacco/alcohol exposure

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) have been causally associated with tobacco and alcohol exposure. However, 10–15% of HNSCC develop in absence of significant carcinogen exposure. Several lines of evidence suggest that the genetic composition of HNSCC varies based on the extent of tobacco/alcohol exposure, however, no genome wide measures have been applied to address this issue. We used comparative genomic hybridization (CGH) to screen for the genetic aberrations in 71 patients with head and neck squamous cell carcinoma and stratified the findings by the status of tobacco/alcohol exposure. RESULTS: Although the median number of abnormalities (9), gains (6) and losses (2) per case and the overall pattern of abnormalities did not vary significantly by the extent of tobacco/alcohol exposure, individual abnormalities segregating these patients were identified. Gain of 1p (p = 0.03) and 3q amplification (p = 0.05) was significantly more common in patients with a history of tobacco/alcohol exposure. CONCLUSIONS: This data suggests that the overall accumulated chromosomal aberrations in head and neck squamous cell carcinoma are not significantly influenced by the severity of tobacco/alcohol exposure with limited exceptions