Identification of epithelial stromal interaction 1 as a novel effector downstream of Krüppel-like factor 8 in breast cancer invasion and metastasis.

Krüppel-like factor 8 (KLF8) is a transcriptional factor critical for metastatic progression of breast cancer. Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells is highly overexpressed in invasive breast carcinomas. The function and regulation of EPSTI1, however, remain largely unknown. In this paper, we report a novel KLF8 to EPSTI1 signaling pathway in breast cancer. Using various expression analyses, we revealed a high co-overexpression of KLF8 and EPSTI1 in invasive human breast cancer cells and patient tumors. Ectopic overexpression of KLF8 in the non-invasive MCF-10A cells induced the EPSTI1 expression, whereas KLF8 knockdown from the invasive, MDA-MB-231 cells decreased the EPSTI1 expression. Promoter activation and binding analyses indicated that KLF8 promoted the EPSTI1 expression by directly acting on the EPSTI1 gene promoter. EPSTI1 knockdown dramatically reduced the KLF8-promoted MCF-10A cell invasion, and ectopic expression of EPSTI1 in the non-invasive MCF-7 cells is sufficient to induce the cell invasion. Experiments using nude mice demonstrated that the ectopic EPSTI1 granted the MCF-7 cells capability of both invasive growth in the breasts and metastasis to the lungs. Using co-immunoprecipitation coupled with mass spectrometry, we discovered that EPSTI1 interacts with the valosin-containing protein (VCP), resulting in the degradation of IκBα and subsequent activation of NF-κB in the nucleus. These findings suggest a novel KLF8 to EPSTI1 to VCP to NF-κB signaling mechanism potentially critical for breast cancer invasion and metastasis.

KLF8 and FAK cooperatively enrich the active MMP14 on the cell surface required for the metastatic progression of breast cancer.

Krüppel-like factor 8 (KLF8) regulates critical gene transcription associated with cancer. The underlying mechanisms, however, remain largely unidentified. We have recently demonstrated that KLF8 expression enhances the activity but not expression of matrix metalloproteinase-2 (MMP2), the target substrate of MMP14. Here, we report a novel KLF8 to MMP14 signaling that promotes human breast cancer invasion and metastasis. Using cell lines for inducible expression and knockdown of KLF8, we demonstrate that KLF8 promotes MMP14 expression at the transcriptional level. Knocking down KLF8 expression inhibited the breast cancer cell invasion both in vitro and in vivo as well as the lung metastasis in mice, which could be rescued by ectopic expression of MMP14. Promoter reporter assays and oligonucleotide and chromatin immunoprecipitations determined that KLF8 activates the human MMP14 gene promoter by both directly acting on the promoter and indirectly via promoting the nuclear translocation of ß-catenin, the expression of T-cell factor-1 (TCF1) and subsequent activation of the promoter by the ß-catenin/TCF1 complex. Inhibition of focal adhesion kinase (FAK) using pharmacological inhibitor, RNA interference or knockout showed that the cell surface presentation of active MMP14 downstream of KLF8 depends on FAK expression and activity. Taken together, this work identified novel signaling mechanisms by which KLF8 and FAK work together to promote the extracellular activity of MMP14 critical for breast cancer metastasis.

Junctures to the therapeutic goal of diabetes mellitus: Experience in a tertiary care hospital of Kolkata.

INTRODUCTION: The World Health Organization has declared India as the "diabetic capital" of the world. In controlling of such chronic, mostly asymptomatic disease, patients' role can't be overemphasized. AIMS: To assess the level of compliance to anti-diabetic therapies and to ascertain the determinants of non-compliance, if any. MATERIALS AND METHODS: A cross-sectional observational study was conducted for 3 months in a diabetic clinic of R G Kar Medical College and Hospital, Kolkata. Data were collected by interviewing the patients, examining their prescriptions and laboratory reports and anthropometry after obtaining informed consent. RESULTS: Blood report at the point of data collection revealed controlled glucose homeostasis in 38.93% patients but evaluation of past 3 months report showed only 24.3% had control over hyperglycemia. Glycemic control was seen to be positively related to short duration of disease, compliance to therapies, and high knowledge about diabetes. Compliance to therapies found in 32.22% of study subjects was in turn associated with short duration of disease. House-wives showed poor compliance; insulin treatment with or without oral-anti-diabetic agent showed better compliance. Knowledge of diabetes was significantly high among higher educated; poor among women, house-wives, and rural people. CONCLUSION: Patient-providers collaboration is to be developed through a patient-centered care model based on the mutual responsibility of both so that each patient is considered in the mesh of his/her other goals of life and helped to promote empowerment to take informed decision for behavioral change conducive to control the disease.

A study on habits of tobacco use among medical and non-medical students of Kolkata.

BACKGROUND: Age-old practice "using tobacco" is a well known major global concern as it victimizes all its lovers by a host of chronic noncommunicable diseases including cancer; all develop very slowly and silently, and can cause premature death. OBJECTIVES: To assess the pattern of tobacco use among the medical and nonmedical college students. MATERIALS AND METHODS: A cross-sectional descriptive study was carried out in Kolkata collecting anonymous data from 515 medical and 349 nonmedical college students of two medical and two general colleges, selected randomly. RESULT: Overall prevalence of tobacco use (18.3% vs 43.6%) and smoking (14.9% vs 40.7%) were significantly less in medical subjects, both across the sex and years of study. Lower rate of tobacco adoption at college level, higher quitting rate, correct knowledge regarding uselessness of filter attached with cigarette, and ill-effects of tobacco consumption were observed among medical participants. More nonmedical subjects were increasingly smoking compared to medical students. Filter-tipped cigarette was the top choice, and smoking was more prevalent mode of use among the nonmedical participants, most (62.3%) of whom were mild users. Curiosity was the top influencing factor for the initiation of tobacco use and two-third users wanted to quit. CONCLUSION: Although the mortal habits was comparatively less among medical students, the medical environment seemed to fail to curb the dreadful practice totally. Thereby it can be recommended that active behavior-changing communication is required for all sections of the society to tear out the social root of the problem instead of unimpressive vague health warnings in vogue.

A study on body mass index (BMI) and some biochemical parameters of the medicos with family history of diabetes mellitus, hypertension and coronary heart disease.

Increasing prevalence of diabetes mellitus (DM), hypertension (HT), coronary heart disease (CHD) is alarming; risk factors are fairly stable, passing fairly well from childhood to adulthood; genetic factors play a role. This is important to know the status of some biochemical parameters viz, fasting plasma glucose level, fasting serum insulin (FI), serum triglyceride (STG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) among the medicos with family history (FH) of DM, HT or CHD and the relationship of biochemical parameters with body mass index (BMI). Mean age of the sample (n=67) was 22 years with 76.12% males and 23.88% females; 44.78%, 29.85% and 19.40% had FH of DM, HT and CHD respectively; 8.96% had the FH of three diseases. High BMI was seen in 62.69% cases; it was significantly high among those with FH of DM (p<0.05) but not significant against HT (p>0.05) or CHD (p>0.05). All had normal fasting plasma glucose level. Positive association existed (a) between BMI with FI, LDL and HDL, FI with LDL and HDL, TG with TC, TC with LDL and HDL, LDL with HDL among those with FH of DM; (b) between BMI with FI, STG and HDL, FI with LDL and HDL, TC with LDL and HDL, LDL with HDL among those with FH of HT; (c) between BMI with FI, STG and HDL, FI with TC, LDL and HDL, TC with LDL and HDL, LDL with HDL among those with FH of CHD. Multiple correlation coefficients (R) also indicated moderate association.

A population based survey of the prevalence and types of glaucoma in rural West Bengal: the West Bengal Glaucoma Study.

AIM: To determine (i) the prevalence of glaucoma in people aged > or =50 years, (ii) the proportions of different types of glaucoma, (iii) the distributions of intraocular pressure and vertical cup disc ratio. METHOD: Population based prevalence survey in rural West Bengal. People aged > or =50 years in randomly selected villages in 24 Parganas South district. The main outcome measures were diagnosis of glaucoma, based on criteria described by the International Society for Geographic and Epidemiological Ophthalmology. RESULTS: 1594 people aged > or =50 years were enumerated in nine villages; 1324 (83.1%) were surveyed and 1269 people adequately examined. 42 definite cases of glaucoma were identified, with prevalence increasing from 2.7% (95% CI 1.7 to 3.7) in people aged 50-59 years to 6.5% (95% CI 0.0 to 14.1) in those aged > or =80 years. The age standardised estimate for the prevalence of all glaucoma in people aged > or =50 years was 3.4%. Only three cases of primary angle closure glaucoma (PACG) were identified, giving a crude ratio of primary open angle glaucoma (POAG) to PACG of more than 10:1. Three people with glaucoma were blind in one eye but none was blind in both eyes. CONCLUSION: Compared to other surveys of glaucoma in India, the age standardised prevalence observed was less than in Hyderabad, but similar to Tamil Nadu and Dhaka. The ratio of POAG to PACG was much higher than found previously, suggesting that PACG may be less prevalent in Bengalis than in Indian populations living in south India. The authors conclude that ophthalmic services in West Bengal should focus on detecting POAG. Since there is still no satisfactory method of screening for POAG, there is no alternative to case detection (opportunistic screening) in eye clinics.

P.C. Sen Memorial best paper award on rural health practice: A study on visual acuity and vitamin A deficiency among primary school students in Naxalbari Village, Darjeeling district of West Bengal.

331 primary school students studying from Nursery classes to Class IV in 2 randomly selected schools in Naxalbari Village in Darjeeling district of West Bengal were tested for visual acuity (VA), Vitamin A deficiency (VAD) and Bitot's spot. 329 students could be tested for visual acuity whereas all 331 students were tested for VAD and Bitot's spot. The prevalence of abnormal Visual Acuity (VA) (VA < 6/9 in any eye) in this study group was 3.65% and it was highest in 7-8 years age group in both the sexes contributing to 75% of the total students having abnormal VA. All these children fell within 50th percentile of weight and height for their respective age and sex. Hindu & ST children accounted for 91.67% & 50% abnormal VA respectively; however, when presence of abnormal VA was compared with its absence between 2 sexes, Hindu and Muslim students and in different castes, no statistically significant differences were found (p > .05). Students of Class-I and Class-II contributed 25% and 50% respectively and together accounted for 75% of abnormal VA. Prevalence of VAD was 8.16%. Among sufferers of VAD Hindus (81.48%) and ST (51.85%) were the main contributors; the differences between presence and absence of VAD in 2 sexes, among 3 religious groups were not statistically significant (p > .05); however, differences among ST and NonSCST groups, and again SC, ST and Non-SCST groups were statistically significant (p < .05). Prevalence of Bitot's spot was 3.63%. Among the students having Bitot's spot, females (58.33%) outnumber the males (41.67%); but the difference between presence and absence of Bitot's spot in 2 sexes was not statistically significant (p > .05). 83.33% each of Hindus and STs had Bitot's spot. No SC and no Muslim student had this spot; the differences between presence and absence of Bitot's spot between Hindu and Christian students were statistically significant (p < .01); similarly when the findings were considered between ST and NonSCST students the difference was found to be statistically highly significant (p < .001).

An evaluation of bed management in a rural hospital adjacent to Indo-Nepal border in West Bengal.

Bed management is one of the important activities for efficient hospital management. The present study on evaluation of bed management in a rural hospital revealed that the total bed capacity could not be utilised. The turnover rate, turnover interval, bed occupancy rate and average length of stay were closely corroborating.

Reproductive health needs and care seeking behaviour of pavement dwellers of Calcutta.

An unabated growth of street dwellers in the city of Calcutta is reported to be due to twin reasons like, migration of rural poor people as well as uncontrolled fertility among these poor settlers of the city. A community-based study on reproductive health, fertility and related care seeking behaviour was studied among a sample of women of child bearing age living on streets of Calcutta. Besides, the quite common conditions like leucorrhoea (28.5%), menstrual irregularities (12.3%), infertility (2.5%) and STDs (1.3%) were also reported. But most of these illnesses (three-fourth) were uncared for, and the remaining one-fourth sought treatment from govemment institutions, private agencies or even from untrained practitioners (quacks). The reproductive behaviour of street dwelling women was characterised by early marriage, teenage pregnancies, and scarce use of contraceptives (32%) as well as frequent abortions (2.8%). Very few pregnant women received adequate antenatal care (3.8%). Coverage of tetanus toxoid immunisation (68.5%) and proper iron and folic acid supplementation (16.7%) were also poor. Whereas, antenatal care was received mostly from government health institutions (71%), home delivery (ie, on street) was a common practice and conducted mostly by untrained birth attendants (51.8%).

Rural people and fine needle aspiration cytology (FNAC)--some findings in North Bengal Medical College, Darjeeling, West Bengal.

A hospital based interdepartmental collaborative study was carried out from 1st July to 30th September, 2000 on 269 rural people residing in six districts of the northern part of West Bengal and attending the Pathology Department in North Bengal Medical College for Fine Needle Aspiration Cytology (FNAC) after being referred from different clinical departments. The objectives of the study were to study some aspects of the outcomes of FNAC among rural people and to suggest for its wider application in rural community through Community Health Centre/Rural Hospital/Block Primary Health Centre. The results shows that Hindus (80.3%) are attending more in number than Muslims (14.13%), Christians (4.83%) and Buddhist (0.74%); 53.54% of the population are in 11-40 years age group. In benign conditions 76.95% are coming from up to 100 kms. of N.B.M.C; people in lower per capita income group of up to Rs.400/- per month are attending twice in number than those in the income groups of Rs.401/- and more per month. In malignancy however people do not think of distance or expenses due to seriousness of the diseases. In 14.5% cases FNAC remains inconclusive whereas in 85.5% cases it provides definite diagnoses.

Improved sidelobe performance of cosine series functions.

The cosine series functions are used extensively for SAW filter design with noniterative techniques. This paper presents improved sidelobe levels of these functions by rigorous application of criteria for minimising the sidelobe peaks. An improvement of 2 dB in sidelobe levels is achieved with respect to the earlier results. A new approach is presented to determine the coefficients of these functions uniquely, which reduces the number of simultaneous equations to be solved to N-1 compared to N equations required to be solved in the earlier method.

Study of the impact of epidemiological factors on intelligence of rural children of 3 to 6 years age group belonging to low socio-economic status.

There are many factors which affect intelligence as well as physical growth of children, although genetic factor plays a prime role but social, environmental and psychological factors influence significantly the physical growth and intelligence of the child and the same can be improved through intervention. Community based studies are therefore useful to understand effect of these factors for future planning. The present study was therefore undertaken in Burdwan district of West Bengal with the objectives of studying level of intelligence of children of 3 to 6 years age group and impact of the factors related to the level of intelligence of these children. 72 children of 3 to 6 years age group were studied, of which 2/3 were either normal or having Grade-I undernutrition and the rest were either Grade-II or Grade-III. A significant positive association was found between DST IQ score (Bharat Raj) and the nutritional grade. Non-formal education also was found to have significant bearing on the IQ level. No significant relationship was however found between DST IQ score and the religion indicating culture independence of the scoring system.

PIP: During January-December 1991 in India, door-to-door visits were made at 59 households with at least one child 3-6 years old in the field practice area of Burdwan Medical College in West Bengal. The researchers wanted to examine the intelligence level of the children and the effect on their intelligence of associated factors such as nutrition, socioeconomic status, and environment. There were 72 children 3-6 years old. Mean family size was 6.9. The houses were in poor condition. 47.5% of families defecated in open fields. 36.11% of the children had either grade II or grade III malnutrition. 66.7% of the children had a Developmental Screening Test (DST) IQ score within the normal range (85-115). 30.6% had borderline scores (68-84). Two children were mildly retarded (52-67). Neither religion nor socioeconomic status influenced the IQ level. The proportion of normal IQ children who have had nonformal schooling was much greater than that of normal IQ children who have not had nonformal schooling (88.6% vs. 45.9%; p 0.01). Children of normal and grade I nutritional status were more likely to have a normal IQ level than those with grade II or grade III malnutrition (75% and 77.3% vs. 57.1% and 20%, respectively; p 0.05). Nonformal education had a significant independent effect on the IQ level (Z = 3.03; p 0.05), while nutritional status did not have a significant independent effect (Z = 1.39; p 0.05). There was a positive significant association between DST IQ score and sitting height (r = 0.27; p 0.05) and head circumference (r = 0.27; p 0.05). These findings indicate the need for a balanced diet and nonformal education to foster child development, especially intelligence, during the first six years of life.

Preventing gastric regurgitation with a ballooned nasogastric tube.

Regurgitation and aspiration of gastric contents remain a major source of morbidity and mortality in the perioperative period. A modified nasogastric tube has been designed with an integral balloon which is inflated in the stomach and impacted, by gentle traction, at the gastro-oesophageal junction, to prevent gastro-oesophageal reflux. Preliminary studies demonstrate its effectiveness in improving the competence of the gastro-oesophageal sphincter.

Relative number and proliferation kinetics of hemopoietic stem cells in the mouse.

A model calculation of the hemopoiesis of the mouse based on known hematologic data leads to the conclusion that approximately 3% of all nucleated bone marrow cells are stem cells (pluripotent plus committed stem cells). By a new 125IUdR labeling technique on radiation chimeras, a relative number of 2%-7% stem cells was determined. In previous studies with test systems for stem cells using colony formation in vivo or in vitro, a relative number of stem cells of at least one order of magnitude lower has been estimated. In this study the stem cells are found to have a turnover time of about 4.3 days in the donor mice. This turnover time remained unchanged even after transfusion of marrow cells into lethally irradiated recipient mice. Radiosensitivity determinations yielded a D0 of 80 rad for stem cells in S-phase and D0 of 185 rad for stem cells distributed throughout the entire cell cycle. The respective extrapolation numbers were 1.23 and 1.14. Experiments using an 3H-TdR suicide technique revealed different cell cycle parameters for bone marrow stem cells seeding to the spleens and to the femurs of lethally irradiated recipients, primarily a shortening of S-phase in cells seeding to femurs. The method described here provides a new approach to hematologic stem cell research.

Nitrous oxide and the middle ear.

A case of hearing deficit following nitrous oxide anaesthesia is reported. The mechanism and time course of nitrous oxide-induced intratympanic pressure changes are described and contrasted with the effects of non-nitrous oxide anaesthesia. The rate of increase is about 10 mm H20/min. The possibility that nitrous oxide may cause displacement of tympanic membrane grafts both outwards and inwards, or disrupt the reconstructed middle ear conducting mechanism, is raised again.