Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression

We present an overview of Runx involvement in regulatory mechanisms that are requisite for fidelity of bone cell growth and differentiation, as well as for skeletal homeostasis and the structural and functional integrity of skeletal tissue. Runx-mediated control is addressed from the perspective of support for biological parameters of skeletal gene expression. We review recent findings that are consistent with an active role for Runx proteins as scaffolds for integration, organization and combinatorial assembly of nucleic acids and regulatory factors within the three-dimensional context of nuclear architecture.     

Successful treatment of systemic and central nervous system lymphomatoid granulomatosis with rituximab

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder with a mortality rate approaching 60% in the first year. The median survival is 14 months from the time of diagnosis. Although a variety of chemotherapeutic regimens have been utilized, there is no standard treatment. Studies have shown that in most cases the malignant cells are B-cells, which induce massive infiltration of reactive T-lymphocytes in the background. The disease is therefore considered as a T-cell rich B-cell lymphoproliferative disorder. We report a case of LYG with pulmonary, hepatic, central and peripheral nervous system involvement that was successfully treated with the anti-CD20 (B-cell) monoclonal antibody, Rituximab.     

Molecular and clinical epidemiology of vancomycin-resistant Enterococcus faecalis

OBJECTIVES: With the recent emergence of vancomycin-resistant (VR) Staphylococcus aureus, subsequent to the suggested transfer of the vanA resistance gene from Enterococcus faecalis, we sought to determine risk factors for acquisition of VR E. faecalis and to evaluate the molecular epidemiology of this less-prevalent and less-studied species of VR enterococcus. METHODS: We compared clinical isolates of VR E. faecalis from 71 patients, collected over 12 years in a large community teaching hospital, with isolates from 126 patients with vancomycin-susceptible E. faecalis. RESULTS: Risk factors for VR E. faecalis acquisition by multivariate analysis were nursing home residence (P = 0.0005), haemodialysis (P = 0.009), decubitus ulcers (P = 0.03) and receipt of parenteral vancomycin (P = 0.0002). Twenty-one percent of VR E. faecalis demonstrated vanA and 79% vanB resistance. The number of VanA isolates increased over time. Molecular analysis showed vanA or vanB in multiple PFGE groups. CONCLUSIONS: The results of this study suggest gene dissemination among some isolates and intra-hospital spread of other isolates. The risk factors identified clearly suggest that VR E. faecalis is a nosocomial pathogen and should be considered in infection control practices. Further surveillance of VR E. faecalis is warranted, due to the potential spread of vancomycin resistance among enterococci and staphylococci.     

Semen quality and reproductive hormones among welders —A preliminary study

Objectives Welders are exposed to intense heat, toxic metals and their oxides and toxic gases during welding, and some of these substances reported to have adverse effects on reproductive organs. Thus, the present study was planned to investigate the sperm quality as well as reproductive hormones among welders exposed to a complex mixture of pollutants. Methods Seventeen welders aged 43.8±12.0 (mean±SD) years with welding exposure of 1 to 10 years or more participated in this study. They were performing are and gas welding in a workshop. Blood (5–6 ml) and semen samples by masturbation were collected from them. Serum was separated and analyzed for reproductive hormones by RIA techniques. Semen was processed for microscopic examination. Results The results of this study indicated that sperm concentration was in the normal range (≥20 million/ml) in all seventeen welders, however, motility, morphology as well as Hypo Osmotic Swelling test (HOS) demonstrated impairment in few welders, indicating deterioration in sperm quality compared to the reported normal reference value. Compared with the normal value of hormones provided in diagnostic kits brochure, follicle stimulating hormone (FSH), leutinizing hormone (LH) and testosterone levels were in the normal range, except in two subjects who showed higher FSH and LH levels and one who showed a lower value of testosterone. Conclusions This study suggests that welding might have had some adverse effects on sperm motility, morphology and physiologic function even though sperm concentration was in the normal range. Hormonal changes did not show any definite pattern, indicating a need for further study.     

Leprosy: otolaryngologist's perspective

A patient with hemi-facial erythematous swelling as a result of borderline leprosy and reversal reaction is reported. This uncommon presentation of the disease poses initial diagnostic difficulties to the otolaryngologist. The otolaryngologist must be familiar with otolaryngologic manifestations of leprosy, since early diagnosis and treatment reduces the risk of transmission of the disease and may avoid permanent nerve damage.     

Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome)

The present authors have previously described a consanguineous Pakistani family with fibular hypoplasia and complex brachydactyly (DuPan syndrome) inherited as an autosomal recessive trait. All affected individuals showed either reductions or absence of bones in the limbs, and appendicular bone dysmorphogenesis with unaffected axial bones. Obligate heterozygote parents were phenotypically normal. Mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene have been reported in two acromesomelic chondrodysplasias (i.e. Hunter-Thompson type and Grebe type) which are phenotypically related to DuPan syndrome. CDMP1, a member of the transforming growth factor beta super-family of secreted signalling molecules, has been reported to regulate limb patterning and distal bone growth. Therefore, the present authors examined genomic DNA from the family with DuPan syndrome for mutations in the CDMP1 gene. Affected individuals were homozygous for a missense mutation, T1322C, in the coding region of the CDMP1 gene. This mutation was not found in 44 control subjects of Pakistani origin. The T1322C change predicts a leu441pro substitution in the mature domain of the CDMP1 protein. This is likely to cause a conformational change in the CDMP1 protein that influences the expression of genes which are required for normal bone development. This finding extends the spectrum of phenotypes produced by defects in the CDMP1 gene.     

Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS

Calcitonin was discovered as a hypocalcemic principal that was initially thought to originate from the parathyroid gland. This view was corrected subsequently, and an origin from the thyroid C cells was documented. The purification and sequencing of various calcitonins soon followed. Calcitonin is a 32-amino-acid-long peptide with an N-terminal disulfide bridge and a C-terminal prolineamide residue. The peptide was shown to potently inhibit bone resorption; however, a direct osteoclastic action of the peptide was confirmed only in the early 1980s. Several osteoclast calcitonin receptors have subsequently been cloned and sequenced. Specific regions of the receptor necessary for ligand binding and intracellular signaling through cyclic AMP and calcium have been identified through systematic deletion mutagenesis and chimeric receptor studies. Calcitonin's potent antiresorptive effect has led to its use in treating Paget's disease of bone, osteoporosis, and hypercalcemia. This review retraces key aspects of the synthesis and structure of calcitonin, its cellular and molecular actions, and its therapeutic uses as they have emerged over the 40 years since its discovery. The review also examines the implications of these findings for future clinical applications as a tribute to early workers to whom credit must be given for creation of an important and expanding field. Notable are the new approaches currently being used to enhance calcitonin action, including novel allosteric activators of the calcitonin receptor, modulation of the release of endogenous calcitonin by calcimimetic agents, as well as the development of oral calcitonins.     

Hypolipidaemic activity of seaweed from Karachi coast

During the present study, ethanol extracts of five seaweed species Solieria robusta, Iyengaria stellata, Colpomenia sinuosa, Spatoglossum asperum and Caulerpa racemosa at 10 mg/ 200 g body weight were tested for their hypolipidaemic activity. All the species significantly decreased the serum total cholesterol, triglyceride and low density lipoprotein cholesterol levels in normal, triton-induced and diet-induced hyperlipidaemic rats. Solieria robusta was found to be the most effective in reducing the lipid profile, particularly in diet-induced hyperlipidaemic rats. A beneficial effect of the ethanol extract of S. asperum was also found on cardiac and liver enzymes in diet-induced hyperlipidaemic rats.