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Biomedical subjects

S Kakar

Publications and source records attributed to S Kakar.

At least 19 recordsLinked to original sources
PubMed2005

Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing.

Recent studies from our laboratory demonstrate that TNF-alpha signaling contributes to the regulation of chondrocyte apoptosis and a lack of TNF-alpha signaling leads to a persistence of cartilaginous callus and delayed resorption of mineralized cartilage. This study examines how delays in the endochondral repair process affect the expression of specific mediators of proteolytic cartilage turnover and vascularization. Simple closed fractures were produced in wild type and TNF-alpha receptor (p55-/-/p75-/-)-deficient mice. Using ribonuclease protection assay (RPA) and microarray analysis, the expression of multiple mRNAs for various angiogenic factors and the metalloproteinase gene family were measured in fracture calluses. The direct actions of TNFalpha on the expression of specific angiogenic factors and metalloproteinases (MMPs) was examined in both cultured callus cells and articular chondrocytes to compare the effects of TNF-alpha in growth cartilage versus articular cartilage. MMPs 2, 9, 13, and 14 were quantitatively the most prevalent metalloproteases and all showed peaks in expression during the chondrogenic period. In the absence of TNF-alpha signaling, the expression of all of these mRNAs was reduced. The angiopoietin families of vascular regulators and their receptors were expressed at much higher levels than the VEGFs and their receptors and while the angiopoietins showed diminished or delayed expression in the absence of TNF-alpha signaling, VEGF and its receptors remained unaltered. The expression of vascular endothelial growth inhibitor (VEGI or TNFSF15) showed a near absence in its expression in the TNF-alpha receptor-deficient mice. In vitro assessment of cultured fracture callus cells in comparison to primary articular chondrocytes showed that TNF-alpha treatment specifically induced the expression of MMP9, MMP14, VEGI, and Angiopoietin 2. These results suggest that TNF-alpha signaling in chondrocytes controls vascularization of cartilage through the regulation of angiopoietin and VEGI factors which play counterbalancing roles in the induction of growth arrest, or apoptosis in endothelial cells. Furthermore, TNF-alpha appears to regulate, in part, the expression of two key proteolytic enzymes, MMP 9 and MMP14 that are known to be crucial to the progression of vascularization and turnover of mineralized cartilage. Thus, TNF-alpha signaling in healing fractures appears to coordinate the expression of specific regulators of endothelial cell survival and metalloproteolytic enzymes and is essential in the transition and progression of the endochondral phase of fracture repair.

Angiogenic Proteins↗
PubMed2002

An auxotrophic pigmented Cryptococcus neoformans strain causing infection of the bone marrow.

Cryptococcosis, caused by an encapsulated fungus, Cryptococcus neoformans, has emerged as a life-threatening infection in HIV-positive individuals and other immunocompromised hosts. This report describes an unusual strain of C. neoformans isolated from an AIDS patient that developed pigment on Sabouraud's medium. The yeast was auxotrophic for adenine due to a deletion in the coding region of ADE2, and was complemented by introduction of a functional copy of the ADE2 gene from C. neoformans. The yeast had an unusual myelotropism that was clinically evident as a pancytopenia with displacement of bone marrow precursors by yeast cells, and it had an unusual spectrum of infection in the human host. This is the first description of a nutritional auxotroph of C. neoformans isolated from a patient.

AIDS-Related Opportunistic Infections↗
PubMed2001

The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision.

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared. Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction. All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity. This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.

Adult↗
PubMed2000

Comparison of PathVysion and INFORM fluorescence in situ hybridization kits for assessment of HER-2/neu status in breast carcinoma.

BACKGROUND: Fluorescence in situ hybridization is advocated for precise assessment of HER-2/neu status in breast carcinoma; however, few objective data compare available kits for clinical laboratories contemplating development of the test. METHODS AND RESULTS: Thirty breast carcinomas were analyzed for HER-2/neu amplification with the PathVysion kit (Vysis, Downers Grove, IL) and INFORM kit (Ventana Medical Systems, Tucson, AZ). Each kit was evaluated for morphology, background staining, technical and interpretation time, and cost. PathVysion detected amplification in seven of 30 cases (23.3%); INFORM detected six of 30 cases (20%). A greater percentage of PathVysion cases showed good morphology and lower background staining than INFORM. Technical and interpretation times, as well as cost, were less with PathVysion than INFORM. CONCLUSION: PathVysion is superior to INFORM because it produces better morphology and less background staining and is faster and less expensive than the INFORM kit. It also includes a chromosome 17 probe that serves as an internal control and enables correction for chromosome 17 aneuploidy.

Breast Neoplasms↗
PubMed2000

HER-2/neu assessment in breast cancer by immunohistochemistry and fluorescence in situ hybridization: comparison of results and correlation with survival.

BACKGROUND: HER-2/neu immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results guide breast cancer therapy; however, few studies compared the results and no published studies have correlated them with patient outcome. METHODS AND RESULTS: We compared results, cost, and turnaround time in 117 archival, invasive breast carcinomas and compared 50-month survival in 65 of these cases using commercial HER-2/neu IHC and FISH assays. Twenty-one of 112 FISH (19%) and 33 of 117 IHC cases (28%) were positive. Concordance was high overall (88%; 98 of 112 cases) and in IHC 3+ cases (88%; 14 of 16 cases) but low in IHC 2+ cases (35%; six of 17 cases). Survival correlated with IHC results in 3+ cases (P =.02) and FISH cases with signal ratio greater than 4.0 (P =.03), but not in IHC 2+ cases (P=.7). Cost and turnaround time were greater for FISH. CONCLUSION: IHC is appropriate for initial HER-2/neu assessment; however, patients with tumors scored less than 3+, particularly those interpreted as 2+, would benefit from FISH to more accurately assess HER-2/neu status and avoid inaccurate prognostication and inappropriate treatment.

Breast Neoplasms↗
PubMed2000

Modulation of the formation of adhesions during the healing of injured tendons.

The formation of restrictive adhesions around the musculotendinous unit after injury is one of the most vexing processes faced by the surgeon. In flexor tendons it has been shown that the synovial tissue is the source of aggressive fibroblasts which contribute to this process. Using a rabbit model, we have examined the effects of treating the synovial sheath with the antimetabolite 5-fluorouracil (5-FU) for five minutes. Inflammatory, proliferative and molecular markers were compared in the response of the treated and control tendons to injury. Compared with a control group we found that the proliferative and inflammatory responses were significantly reduced (p < 0.001) in the treated tendons. Not only was there a reduction in the cellular and cytokine response, but there also was a significant (p < 0.001) reduction in the level of activity of the known pro-scarring agent, transforming growth factor beta 1 (TGF-beta1). These pilot studies indicate that the formation of restrictive adhesions may be modulated using a simple single-touch technique in the hope of producing a better return of function.

Animals↗
PubMed1999

Vibrio cholerae O1 serotype Ogawa in a neonate.

In India, cholera is endemic and affects usually the 3 to 5-year-old age group. There have been occasional reports in the neonatal period with Vibrio cholerae O139 Bengal. We report here a case of Vibrio cholerae O1 diarrhea in a 2-day-old, breastfed male, who had been delivered in the hospital and developed severe dehydration.

Humans↗
PubMed1999

Profound thrombocytopenia in Plasmodium vivax malaria.

In India, malaria is endemic and commonly caused by Plasmodium vivax and P. falciparum. Thrombocytopenia is a common finding in falciparum infection but is rare in P. vivax infection. We report profound thrombocytopenia in a 43-year-old female patient due to P. vivax infection. The platelet count was as low as 5 x 10(9)/liter, such severe thrombocytopenia has never been reported in vivax malaria.

Adult↗
PubMed1998

Differential cellular response within the rabbit tendon unit following tendon injury.

The cellular changes in the epitenon, endotenon and synovial sheath were investigated in a rabbit model after a partial transverse laceration was made on the plantar aspect of the flexor digitorum profundus proximal to the synovial sheath (which was not injured). Fibroblasts, macrophages and mast cells within the epitenon, endotenon and synovial sheath were counted on electron micrographs. The epitenon and uninjured synovial sheath became engorged with fibroblasts and macrophages following injury. The number of synovial fibroblasts showed the greatest increase during the first week after injury. In comparison, the endotenon exhibited a delay in cellular response with initial apoptosis, as judged by positive P53 staining. However, hypercellular activity was seen within the endotenon at 12 weeks postoperatively.

Animals↗
PubMed1998

Anatomical description and frequencies of bony projections on the cerebral aspect of the petromastoid part of the temporal bone in dry adult human skulls.

A morphological peculiarity was observed in the form of bony projections on the upper part of the medial border of the groove for the sigmoid sulcus on the internal surface of the mastoid part of the temporal bones. In a study on 636 temporal regions of 318 dry unsexed adult human skulls of Indian origin, 101 (15.9%) temporal bones exhibited these elevations. These ranged from being inconspicuous tubercles to well-defined sharp spines. In 73 (72.3%) cases, a projection was present unilaterally, more commonly on the right side and in 28 (27.7%) it was bilateral. A subjective assessment of the size showed the projections to be small (70; 69.3%), medium (16; 15.8%) and large (15; 14.8%).

Adult↗
PubMed1995

Clinical work and cultural imagination.

With illustrations from clinical experience in India, this paper discusses the question of the cultural rootedness of psychoanalysis as a therapeutic method and some of the cultural differences, chiefly, the dominance of the theme of "maternal enthrallment," both in Indian cultural imagination and in clinical work with male patients.

Adult↗
PubMed1991

The hydration of actin.

The hydration of actin was studied by differential scanning calorimetry between -30 degrees C and 30 degrees C and by thermogravimetric analysis. The differential scanning calorimetry provided the freezable water content of G- and F-actin as a function of concentration, and the thermogravimetric analysis measured the total water content. The difference between the two yielded the nonfreezable water content (bound water) as a function of concentration. The nonfreezable water content of G-actin was higher than the F-actin over the whole concentration range from 1-40% actin.

Actins↗