Characterization of functional domains within Smad4/DPC4.

Smad proteins are a family of highly conserved, intracellular proteins that signal cellular responses downstream of transforming growth factor-beta (TGF-beta) family serine/threonine kinase receptors. One of these molecules, Smad4, originally identified as the candidate tumor suppressor gene dpc-4, reconstitutes TGF-beta- and activin-dependent transcriptional responses in Smad4 null cell lines and interacts in a ligand-dependent manner with other Smad family members in both TGF-beta, activin, and bone morphogenetic protein-2/-4 pathways. Here, we used an assay based on the restoration of ligand-dependent transcriptional responses in a Smad4 null cell line to characterize functional domain structures within Smad4. We showed that restoration of TGF-beta-induced transcriptional responses by Smad4 was inhibited by co-transfection with a kinase dead TGF-beta type II receptor and that constitutive activation was blocked with TGF-beta neutralizing antibodies, confirming the essential role of Smad4 in TGF-beta signaling. Using a series of Smad4 mutation, deletion, and Smad1/Smad4 chimera constructs we identified a 47-amino acid deletion within the middle-linker region of Smad4 that is essential for the mediation of signaling responses. In addition, we showed that the NH2-terminal domain of Smad4 augments ligand-dependent activation associated with the middle-linker region, indicating that there is a distinct ligand-response domain within the N terminus of this molecule.

Cancer profile in eastern Rajasthan.

A study to determine the pattern of various malignancies in Eastern Rajasthan was conducted for the year 1990 by Cancer Registry, S.M.S. Medical College, Jaipur. This is the first study of its kind from this region where an effort has been made to put the cancer profile in East Rajasthan in perspective. A total of 2509 histologically proven cancer cases were recorded from the various government and private hospitals in this region. There were 1443 males and 1066 females. Maximum number of cases were seen in the 6th and 5th decade. Genital tract cancer (21%) formed the largest overall group of cancers. When combined with the urinary system (7.6%)--the uro-genital tract cancers (28.7%) formed almost one-third of all cancers in this region. Cancer of the prostate (11.40%) and urinary bladder (9.1%) in males recorded the highest incidence in the country. Cancer of the female breast (19.4%) surpassed cancer cervix (18.2%). The frequency of penile, testicular, bone, skin, anorectal cancers and lymphoma was on the higher side. Whereas the incidence of stomach, oesophagus and lung cancer was on the lower side. An urgent need is felt to study the various aetiological factors responsible for these significant variations in Eastern Rajasthan.

Effect of zinc administration on seminal zinc and fertility of oligospermic males.

Fourteen infertile males (age 24-45 years; married over 2 years) with idiopathic oligospermia (sperm count less than 40 millions/ml) were investigated for the effect of oral zinc sulphate (220 mg) for 4 months on their serum and seminal zinc levels, and seminal parameters. With zinc administration serum zinc levels remained essentially unaffected, however, seminal zinc levels increased significantly. There was significant improvement in sperm count, number of progressively motile and normal spermatozoa, and acid phosphates activity. Wives of 3 patients conceived. Observations suggest that zinc has potential to be used in male infertility. However, further studies are warranted.

Lung function tests in Rajasthani subjects.

Various lung volumes and ventilatory tests (TV, ERV, IC, MV, MVV, VC, FEV1, MMFER and PEFR) were determined and BR, DI and AVI (Air velocity Index) calculated in 241 Rajasthani subjects of either sex ranging from 17 to 40 years of age. Most of the values (Mean +/- SEM) are higher in males than in females, and also higher in the younger age groups (17 to 27 years) than in the older age groups (28 to 40 years) for the same sex.