Large Congenital Epulis: A Neonatal Tumour with Striking Appearance, but Simple Management.

Background Congenital epulis is a benign tumor of upper gingiva. Larger lesions interfere with mouth closing and normal feeding and may obstruct airways. We present a neonate with a large epulis. Case Report: A full term 3 kg 5 days female baby had a 20 cm × 15 cm gingival mass protruding from the oral cavity, connected by a pedicle attached to right upper gingiva (Figure 1). Multiple trophic ulcers had developed in the mass after birth. Mouth closing and normal feeding were hampered. The mass was excised surgically and baby improved. Conclusion: A large congenital epulis, though worrisome to parents, can be satisfactorily managed by surgical excision and has a good prognosis.

Evolution and biogeography of Memecylon.

PREMISE: The woody plant group Memecylon (Melastomataceae) is a large clade occupying diverse forest habitats in the Old World tropics and exhibiting high regional endemism. Its phylogenetic relationships have been previously studied using ribosomal DNA with extensive sampling from Africa and Madagascar. However, divergence times, biogeography, and character evolution of Memecylon remain uninvestigated. We present a phylogenomic analysis of Memecylon to provide a broad evolutionary perspective of this clade. METHODS: One hundred supercontigs of 67 Memecylon taxa were harvested from target enrichment. The data were subjected to coalescent and concatenated phylogenetic analyses. A timeline was provided for Memecylon evolution using fossils and secondary calibration. The calibrated Memecylon phylogeny was used to elucidate its biogeography and ancestral character states. RESULTS: Relationships recovered by the phylogenomic analyses are strongly supported in both maximum likelihood and coalescent-based species trees. Memecylon is inferred to have originated in Africa in the Eocene and subsequently dispersed predominantly eastward via long-distance dispersal (LDD), although a reverse dispersal from South Asia westward to the Seychelles was postulated. Morphological data exhibited high levels of homoplasy, but also showed that several vegetative and reproductive characters were phylogenetically informative. CONCLUSIONS: The current distribution of Memecylon appears to be the result of multiple ancestral LDD events. Our results demonstrate the importance of the combined effect of geographic and paleoclimatic factors in shaping the distribution of this group in the Old World tropics. Memecylon includes a number of evolutionarily derived morphological features that contribute to diversity within the clade.

Novel mechanism of negative regulation of 1,25-dihydroxyvitamin D3-induced 25-hydroxyvitamin D3 24-hydroxylase (Cyp24a1) Transcription: epigenetic modification involving cross-talk between protein-arginine methyltransferase 5 and the SWI/SNF complex.

The SWI/SNF chromatin remodeling complex facilitates gene transcription by remodeling chromatin using the energy of ATP hydrolysis. Recent studies have indicated an interplay between the SWI/SNF complex and protein-arginine methyltransferases (PRMTs). Little is known, however, about the role of SWI/SNF and PRMTs in vitamin D receptor (VDR)-mediated transcription. Using SWI/SNF-defective cells, we demonstrated that Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF complex, plays a fundamental role in induction by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) of the transcription of Cyp24a1 encoding the enzyme 25-hydroxyvitamin D3 24-hydroxylase involved in the catabolism of 1,25(OH)2D3. BRG1 was found to associate with CCAAT-enhancer-binding protein (C/EBP) ß and cooperate with VDR and C/EBPß in regulating Cyp24a1 transcription. PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcription and mRNA expression. Our findings indicate the requirement of the C/EBP site for the inhibitory effect of PRMT5 via its methylation of H3R8 and H4R3. These findings indicate that the SWI/SNF complex and PRMT5 may be key factors involved in regulation of 1,25(OH)2D3 catabolism and therefore in the maintenance of calcium homeostasis by vitamin D. These studies also define epigenetic events linked to a novel mechanism of negative regulation of VDR-mediated transcription.

Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines.

Repeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018-19 (N = 723) and 2019-20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.

FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis.

The Forkhead transcription factor FoxO1 inhibits through its expression in osteoblasts ß-cell proliferation, insulin secretion, and sensitivity. At least part of the FoxO1 metabolic functions result from its ability to suppress the activity of osteocalcin, an osteoblast-derived hormone favoring glucose metabolism and energy expenditure. In searching for mechanisms mediating the metabolic actions of FoxO1, we focused on ATF4, because this transcription factor also affects glucose metabolism through its expression in osteoblasts. We show here that FoxO1 co-localizes with ATF4 in the osteoblast nucleus, and physically interacts with and promotes the transcriptional activity of ATF4. Genetic experiments demonstrate that FoxO1 and ATF4 cooperate to increase glucose levels and decrease glucose tolerance. These effects result from a synergistic effect of the two transcription factors to suppress the activity of osteocalcin through up-regulating expression of the phosphatase catalyzing osteocalcin inactivation. As a result, insulin production by ß-cells and insulin signaling in the muscle, liver and white adipose tissue are compromised and fat weight increases by the FoxO1/ATF4 interaction. Taken together these observations demonstrate that FoxO1 and ATF4 cooperate in osteoblasts to regulate glucose homeostasis.

Literature mining of host-pathogen interactions: comparing feature-based supervised learning and language-based approaches.

MOTIVATION: In an infectious disease, the pathogen's strategy to enter the host organism and breach its immune defenses often involves interactions between the host and pathogen proteins. Currently, the experimental data on host-pathogen interactions (HPIs) are scattered across multiple databases, which are often specialized to target a specific disease or host organism. An accurate and efficient method for the automated extraction of HPIs from biomedical literature is crucial for creating a unified repository of HPI data. RESULTS: Here, we introduce and compare two new approaches to automatically detect whether the title or abstract of a PubMed publication contains HPI data, and extract the information about organisms and proteins involved in the interaction. The first approach is a feature-based supervised learning method using support vector machines (SVMs). The SVM models are trained on the features derived from the individual sentences. These features include names of the host/pathogen organisms and corresponding proteins or genes, keywords describing HPI-specific information, more general protein-protein interaction information, experimental methods and other statistical information. The language-based method employed a link grammar parser combined with semantic patterns derived from the training examples. The approaches have been trained and tested on manually curated HPI data. When compared to a naïve approach based on the existing protein-protein interaction literature mining method, our approaches demonstrated higher accuracy and recall in the classification task. The most accurate, feature-based, approach achieved 66-73% accuracy, depending on the test protocol.

Exploring the human microbiome - A step forward for precision medicine in breast cancer.

BACKGROUND: The second most frequent cancer in the world and the most common malignancy in women is breast cancer. Breast cancer is a significant health concern in India with a high mortality-to-incidence ratio and presentation at a younger age. RECENT FINDINGS: Recent studies have identified gut microbiota as a significant factor that can have an influence on the development, treatment, and prognosis of breast cancer. This review article aims to describe the influence of microbial dysbiosis on breast cancer occurrence and the possible interactions between oncobiome and specific breast cancer molecular subtypes. The review further also discusses the role of epigenetics and diet/nutrition in the regulation of the gut and breast microbiome and its association with breast cancer prevention, therapy, and recurrence. Additionally, the recent technological advances in microbiome research, including next-generation sequencing (NGS) technologies, genome sequencing, single-cell sequencing, and microbial metabolomics along with recent advances in artificial intelligence (AI) have also been reviewed. This is an attempt to present a comprehensive status of the microbiome as a key cancer biomarker. CONCLUSION: We believe that correlating microbiome and carcinogenesis is important as it can provide insights into the mechanisms by which microbial dysbiosis can influence cancer development and progression, leading to the potential use of the microbiome as a tool for prognostication and personalized therapy.

Proceedings of the 3rd Indian Cancer Genome Atlas Conference 2022: Biobanking to Omics: Collecting the Global Experience.

On January 13th and 14th 2022, the Center for Translational Cancer Research organized the virtual third Indian Cancer Genome Atlas (ICGA) Conference 2022 "Biobanking to Omics - Collecting the Global Experience." This conference was planned as the steppingstone to help ICGA understand the road ahead and the probable roadblocks in its preparatory phase as ICGA begins to streamline the tumor tissue biobanking and multi-omics efforts in the Indian subcontinent. The first day of the conference was dedicated to updates on the current status of ICGA, the future prospect, and the global understanding of multi-omics efforts. The key highlights included two keynote speeches by Dr Wui Jin Koh, Senior Vice President and Chief Medical Office, National Comprehensive Cancer Network, and by Dr Christina Curtis, Associate Professor, Stanford University School of Medicine. The first day ended with an intriguing panel discussion on "ICGA updates and Future Steps." The second day focused on biobanking practices across the globe and several aspects of biobank setup such as infrastructure, maintenance, quality control, patient consent, and lessons learned from established biobanking setups. The talk by Rosita Kammler, Head, Translational Research Coordination, International Breast Cancer Study Group, Switzerland, and Ruhul Amin, Director, Bangladesh Medical Research Council were the key highlights. The second day also ended with an engaging panel discussion on "Tumor tissue biobanking - national and international perspectives." Overall, the conference was well received and had good attendance from national and international students, researchers, and faculty from academia as well as industry.

Therapeutic mammoplasty: a "wise" oncoplastic choice-lessons from the largest single-center cohort from Asia.

Introduction: The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM. Methods: All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures. Results: The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1-pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains. Conclusion: We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.

Correlation of Histomorphological Findings with Bacteriological Index in Leprosy Patients.

BACKGROUND & OBJECTIVE: Leprosy is characterized by various clinicopathological forms depending on the host's body. Therefore, the correlation of histopathological findings with bacteriological index is helpful in diagnosing, classification, and monitoring the treatment. We aimed to analyze the histomorphological findings correlation with the bacteriological index in different types of leprosy. Then, study the histopathological spectrum of leprosy. METHODS: We carried out a histomorphological study of skin biopsies obtained from 100 new patients tested clinically in OPD (Out Patients Department) on the basis and calculation of bacteriological index on a slit-skin smear. The histomorphological findings correlation with the bacteriological index was to be found in different types of leprosy. RESULTS: In the histopathological studies, 52% of the patients were diagnosed with borderline tuberculoid (BT) followed by 20% with borderline lepromatous (BL), 13% with lepromatous leprosy (LL), 8% with tuberculoid (TT), 4% with histoid Hansen's disease, and 3% with mid-borderline (BB). On the clinical and histopathological examinations, correlation was found for 80% of the cases. Considering the correlation of histopathological features with the bacteriological index, 63% of the cases showed good correlation which was comparable with that of other studies. CONCLUSION: Because of the underlying symptoms of leprosy, there is a difference between different types of leprosy and the clinical and environmental perceptions. Thus, the correlation of clinical, histopathological, and bacteriological indices could be more helpful in the diagnosis of leprosy rather than considering only one parameter.

Dual roles for the variable domain in protein trafficking and host-specific recognition of Heterodera glycines CLE effector proteins.

*Soybean cyst nematodes (Heterodera glycines) produce secreted effector proteins that function as peptide mimics of plant CLAVATA3/ESR (CLE)-like peptides probably involved in the developmental reprogramming of root cells to form specialized feeding cells called syncytia. *The site of action and mechanism of delivery of CLE effectors to host plant cells by the nematode, however, have not been established. In this study, immunologic, genetic and biochemical approaches were used to reveal the localization and site of action of H. glycines-secreted CLE proteins in planta. *We present evidence indicating that the nematode CLE propeptides are delivered to the cytoplasm of syncytial cells, but ultimately function in the apoplast, consistent with their proposed role as ligand mimics of plant CLE peptides. We determined that the nematode 12-amino-acid CLE motif peptide is not sufficient for biological activity in vivo, pointing to an important role for sequences upstream of the CLE motif in function. *Genetic and biochemical analysis confirmed the requirement of the variable domain in planta for host-specific recognition and revealed a novel role in trafficking cytoplasmically delivered CLEs to the apoplast in order to function as ligand mimics.

Discovery of Potent, Selective, and State-Dependent NaV1.7 Inhibitors with Robust Oral Efficacy in Pain Models: Structure-Activity Relationship and Optimization of Chroman and Indane Aryl Sulfonamides.

Voltage-gated sodium channel NaV1.7 is a genetically validated target for pain. Identification of NaV1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent NaV1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over NaV1.5, and CYP2C9 inhibition. The lead molecules 13, 29, 32, 43, and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.

A Prospective Clinicoendoscopic Follow-up Study in Young Patients with Peptic Ulcer Perforation at a Tertiary Institute in Central India.

BACKGROUND: Perforation peritonitis is one of the commonest encountered emergencies in the surgery casualty. This study was conducted with the aim of identifying risk factors in peptic ulcer disease (PUD) in young patients. MATERIALS AND METHODS: Seventy patients were evaluated in this study and were followed up with clinical examination and endoscopy at 8 weeks and 6 months. RESULTS: Out of the total 70 patients, there was a mortality of 5 patients and 7 patients were lost to follow-up. Out of the remaining 57 patients, 56 were men and 1 was a woman. Maximum patients were from the age group of 35-40 years. The patients were categorized on the basis of their clinical symptoms and endoscopy results at the follow-up of 6 months in 4 categories-21 patients having an active ulcer and symptomatic, 15 patients having active ulcer but no symptoms, 16 patients who were asymptomatic and without an active ulcer and 5 patients nonulcer dyspepsia. CONCLUSION: Postoperative treatment with H2 blockers or proton pump inhibiters along with anti-Helicobacter pylori regimen should be prescribed for all patients with peptic ulcer perforation. Routine endoscopic examination of such patients should also form a part of the follow-up to look for ulcer healing postoperatively. HOW TO CITE THIS ARTICLE: Jahagirdaar D, Bomanwar N, Joshi S. A Prospective Clinicoendoscopic Follow-up Study in Young Patients with Peptic Ulcer Perforation at a Tertiary Institute in Central India. Euroasian J Hepato-Gastroenterol 2019;9(2):91-95.

Immunomodulatory actions of a Polynesian herb Noni (Morinda citrifolia) and its clinical applications.

Morinda citrifolia (Noni) is a popular traditional medicinal plant consumed in various forms in several countries around the world as a complementary and alternative treatment due to its established health benefits. Noni is rich in bioactive substances and has significantly exhibited pro-oxidant and immunomodulatory effects. In this review, we highlight the pharmacological basis related to the phytochemicals and polysaccharides present in Noni and its potential therapeutic effects. We screened electronic databases such as PubMed, Google Scholar, Scopus for scientific literature. Our results indicate that Noni is beneficial for various diseases with its crude extracts showing therapeutic benefit for a wide range of pathological diseases. We believe that further pharmacological and toxicological studies in addition to well-designed controlled clinical trials can validate Noni to be an effective and novel natural product for prophylactic and therapeutic use of several diseases.

Underdetection of laboratory-confirmed influenza-associated hospital admissions among infants: a multicentre, prospective study.

BACKGROUND: Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants. METHODS: The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015-16 and 2016-17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period (2015-16) in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses. FINDINGS: Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenza-positive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2·6 (95% CI 2·0-3·6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis. INTERPRETATION: If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes. FUNDING: US Centers for Disease Control and Prevention.

Vitamin D and multiple sclerosis.

Vitamin D is a principal regulator of calcium homeostasis. However, recent evidence has indicated that vitamin D can have numerous other physiological functions including inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells and protection against certain immune mediated disorders including multiple sclerosis (MS). The geographic incidence of MS indicates an increase in MS with a decrease in sunlight exposure. Since vitamin D is produced in the skin by solar or UV irradiation and high serum levels of 25-hydroxyvitamin D (25(OH)D) have been reported to correlate with a reduced risk of MS, a protective role of vitamin D is suggested. Mechanisms whereby the active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) may act to mediate this protective effect are reviewed. Due to its immunosuppressive actions, it has been suggested that 1,25(OH)(2)D(3) may prevent the induction of MS.

Carboxymethyl cellulose-rosin gum hybrid nanoparticles: An efficient drug carrier.

Adequate release of 5-ASA in colon is challenging as it easily permeates at the acidic pH of the upper gastrointestinal tract. Targeting delayed release of 5-ASA at acidic pH, Carboxymethyl cellulose-rosin gum hybrid nanoparticles (CRNP3) with an average size of 267nm have been crafted through nanoprecipitation method. CRNP3 was extensively characterized using Fourier Transform Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and particle size analysis based on dynamic light scattering. Colon specific targeted in-vitro release of 5­Aminosalicylic acid from CRNPs was monitored in simulated gastric (SGF) and intestinal (SIF) fluids. The release rate was very slow in first 2h in SGF, while in SIF, it was greater and 72% drug was released in a controlled manner during the time span of 12h in contrast to native carboxymethyl cellulose or rosin gum for which 100% release was accomplished within 5h or 8h respectively. The delayed release from CRNPs is attractive for enhancing the bioavailability of drug in colon. The drug release followed zero-order kinetics and non-Fickian diffusion mechanism.

Synthesis of Aloevera/Acrylonitrile based Nanoparticles for targeted drug delivery of 5-Aminosalicylic acid.

Aloevera (AV) polysaccharide/acrylonitrile (AN) nanoparticles (AVANp4 of ∼50nm size) have been crafted via free radical polymerization method using persulfate/ascorbic acid (KPS/AA) and methylenebisacrylamide (MBA) as the redox initiator and crosslinker respectively. AVANp4 was extensively characterized using FTIR, SEM, TEM, XRD, and Thermal analysis (TGA & DTG). Inclusion of AN in AV polysaccharide has been evidenced by nitrile stretching peak at 2244cm-1 in FTIR spectrum of AVANp4. Colon specific targeted in-vitro release of 5-Aminosalicylic acid from AVANp4 has been studied in pH 1.2 and pH 7.4 buffer solutions at 37°C. The controlled release was witnessed up to 48h for AVANp4 in contrast to AV for which the release exhausted within 7-8h in both the buffers. The delayed release of the drug from AVANp4 is attractive since it can allow the drug to reach colon rather than being released in the upper part of the gastrointestinal tract.

Vitamin D: molecular mechanism of action.

Vitamin D maintains calcium homeostasis and is required for bone development and maintenance. Recent evidence has indicated an interrelationship between vitamin D and health beyond bone, including effects on cell proliferation and on the immune system. New developments in our lab related to the function and regulation of target proteins have provided novel insights into the mechanisms of vitamin D action. Studies in our lab have shown that the calcium-binding protein, calbindin, which has been reported to be a facilitator of calcium diffusion, also has an important role in protecting against apoptotic cell death in different tissues including protection against cytokine destruction of osteoblastic and pancreatic beta cells. These findings have important implications for the therapeutic intervention of many disorders including diabetes and osteoporosis. Recent studies in our laboratory of intestinal calcium absorption using calbindin-D(9k) null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inducible epithelial calcium channel, TRPV6, provide evidence for the first time of calbindin-D(9k) and TRPV6 independent regulation of active calcium absorption. Besides calbindin, the other major target of 1,25(OH)(2)D(3) in intestine and kidney is 25(OH)D(3) 24 hydroxylase (24(OH)ase), which is involved in the catabolism of 1,25(OH)(2)D(3). In our laboratory we have identified various factors that cooperate with the vitamin D receptor in regulating 24(OH)ase expression including C/EBP beta, SWI/SNF (complexes that remodel chromatin using the energy of ATP hydrolysis) and the methyltransferases, CARM1 and G9a. Evidence is also presented for C/EBP beta as a nuclear coupling factor that coordinates regulation of osteopontin by 1,25(OH)(2)D(3) and PTH. Our findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH)(2)D(3) mediates its multiple biological effects.

Tumoral calcinosis--clinicopathological study of five cases.

Five cases of tumoral calcinosis were studied during the period of January-february 1999 in MIMER medical college, Talegaon, a rural place 35kms. from Pune. All the Five patients were females residing in nonendemic area for Dracunculosis. They were from 5th-6th decade. They were otherwise healthy and had normal serum calcium and phosphorus levels and no eosinophilia. All had large, hard subcutaneous lump around hip joint. The skin overlying the swelling was normal. Histologically all cases showed similar morphology, the lesions were composed of large and small deposits of calcium. The foreign-body giant cell reaction was seen in two cases. There were no eosinophils and lymphocytes. On multiple sectioning none of the cases revealed any evidence of dead or living parasite. Old and recent necrosis was absent. These cases are presented since the condition is comparatively rare and it appeared in crops in our Institute.