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Biomedical subjects

M Sundaram

Publications and source records attributed to M Sundaram.

At least 91 records · Page 5Linked to original sources
PubMed1996

Control and integration of cell signaling pathways during C. elegans vulval development.

Vulval development in the Caenorhabditis elegans hermaphrodite represents a simple, genetically tractable system for studying how cell signaling events control cell fate decisions. Current models suggest that proper specification of vulval cell fates relies on the integration of multiple signaling systems, including one that involves a receptor tyrosine kinase (RTK)-->Ras-->mitogen activated protein kinase (MAPK) cascade and one that involves a LIN-12/Notch family receptor. In this review, we first discuss how genetic strategies are being used to identify and analyze components that control vulval cell fate decisions. We then describe the different signaling systems that have been elucidated and how they relate to one another. Finally, we highlight several recently characterized genes that encode positive regulators, negative regulators or potential targets of the RTK-->Ras-->MAPK cascade involved in vulval induction.

Animals↗
PubMed1996

Chronic recurrent multifocal osteomyelitis: an evolving clinical and radiological spectrum.

OBJECTIVE: To describe unusual clinical and radiological features in patients with chronic recurrent multifocal osteomyelitis (CRMO). DESIGN AND SUBJECTS: Based on radiographic and microscopic findings, three patients were prospectively diagnosed as having chronic recurrent multifocal osteomyelitis (CRMO). They form the basis of this report because of either the unusualness of the clinical presentation, hitherto undescribed associated diseases or the unusual age of presentation and sites of lesions. RESULTS: One patient developed pyoderma gangrenosum at the site of one of the skeletal lesions and then went on to develop ulcerative proctitis. A second patient presented with a soft tissue mass, which on MRI mimicked a sarcoma. The final patient presented with lesions in the wrist and phalanges of the toes at the unusual age of 38. None of the patients was treated with steroids or antibiotics for the skeletal lesions. Steroids were administered to one patient for treatment of pyoderma gangrenosum. CONCLUSIONS: The pattern and distribution of skeletal lesions in CRMO are well recognized in the pediatric age group. The unusual clinical and/or radiological features discussed herein suggests that this is a disease that continues to evolve with a broader spectrum of features than recognized.

Adult↗
PubMed1996

A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans.

Sex myoblast migration in the Caenorhabditis elegans hermaphrodite represents a simple, genetically amenable model system for studying how cell migration is regulated during development. Two separable components of sex myoblast guidance have been described: a gonad-independent mechanism sufficient for the initial anterior migration to the mid-body region, and a gonad-dependent mechanism required for precise final positioning (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041-1052). Here, we demonstrate a role for a Ras-mediated signal transduction pathway in controlling sex myoblast migration. Loss-of-function mutations in let-60 ras, ksr-1, lin-45 raf, let-537/mek-2 or sur-1/mpk-1 cause defects in sex myoblast final positions that resemble those seen in gonad-ablated animals, while constitutively active let-60 ras(G13E) trans-genes allow fairly precise positioning to occur in the absence of the gonad. A mosaic analysis demonstrated that let-60 ras is required within the sex myoblasts to control proper positioning. Our results suggest that gonadal signals normally stimulate let-60 ras activity in the sex myoblasts, thereby making them competent to sense or respond to positional cues that determine the precise endpoint of migration. let-60 ras may have additional roles in sex myoblast guidance as well. Finally, we have also investigated genetic interactions between let-60 ras and other genes important for sex myoblast migration, including egl-15, which encodes a fibroblast growth factor receptor tyrosine kinase (D. L. DeVore, H. R. Horvitz and M. J. Stern (1995) Cell 83, 611-623). Since mutations reducing Ras pathway activity cause a different phenotype than those reducing egl-15 activity and since constitutive Ras activity only partially suppresses the migration defects of egl-15 mutants, we argue that let-60 ras and egl-15 do not act together in a single linear pathway.

Animals↗
PubMed1996

Surface osteomas of the appendicular skeleton.

OBJECTIVE: This study describes the radiographic, CT, and MR imaging features of surface osteomas of the appendicular skeleton in four patients without Gardner's syndrome or tuberous sclerosis and reviews the incidence and management options of this uncommon tumor. CONCLUSION: On imaging (best seen on CT), the osteomas were homogeneously dense-as dense at the periphery as the base-and without an accompanying soft-tissue mass, cortical destruction, or intramedullary invasion. The margins of each osteoma were smooth or smoothly lobulated. When the correct diagnosis was considered in two patients, close clinical follow-up or marginal excision were the management options chosen. Histologic examination of the tumors revealed dense sclerotic lamellar bone with haversian systems that showed features similar to those of normal cortical bone. During a follow-up period of 6 months to 5 years, patients have had no local recurrences or metastases.

Adult↗
PubMed1995

The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction.

Vulval induction in C. elegans is controlled by a highly conserved signaling pathway similar to the RTK-Ras-MAPK cascade in mammals. By screening for suppressors of the Multivulva phenotype caused by an activated let-60 ras allele, we isolated mutations in a gene, ksr-1, that acts as a positive modifier of vulval induction and is required for at least two other let-60 ras-mediated processes. Although ksr-1 mutations do not perturb vulval induction in an otherwise wild-type background, they have very strong effects on vulval induction in genetic backgrounds where Ras pathway activity is constitutively activated or compromised, suggesting that ksr-1 activity is required for maximal stimulation of vulval fates by the Ras pathway. Genetic epistasis analysis suggests that ksr-1 acts downstream of or in parallel to let-60 ras. We cloned ksr-1 and have shown that it encodes a novel putative protein kinase related to the Raf family of Ser/Thr kinases.

Amino Acid Sequence↗
PubMed1995

Appendicular metastatic prostate cancer simulating osteosarcoma, Paget's disease, and Paget's sarcoma.

Skeletal metastases from prostate cancer is common and usually do not pose a diagnostic dilemma. This study reviews radiographic appearances of prostatic metastases to the appendicular skeleton in four patients where the appearances simulated osteosarcoma, Paget's disease and Paget's sarcoma. Prostatic metastases to long bones can produce appearances considered characteristic of other lesions and suggest misleading alternative diagnoses.

Aged↗
PubMed1995

MR imaging of benign soft-tissue masses.

Benign masses outnumber sarcomas. The use of MR imaging for the indeterminate soft-tissue mass has during the past decade permitted radiologists to name the soft-tissue mass or provide a succinct differential diagnosis. This article reviews the identification of benign masses based on signal intensity, location, morphologic characteristics, and other features. The importance of approaching every "indeterminate" mass after MR imaging as malignant until proved otherwise is emphasized, as is the fact that despite the accessibility of the mass, a biopsy should not be done without prior consultation with an orthopedic oncologist.

Biopsy↗