Indoor concentrations of nitrogen dioxide and sulfur dioxide from burning solid fuels for cooking and heating in Yunnan Province, China.

The Chinese national pollution census has indicated that the domestic burning of solid fuels is an important contributor to nitrogen dioxide (NO2 ) and sulfur dioxide (SO2 ) emissions in China. To characterize indoor NO2 and SO2 air concentrations in relation to solid fuel use and stove ventilation in the rural counties of Xuanwei and Fuyuan, in Yunnan Province, China, which have among the highest lung cancer rates in the nation, a total of 163 participants in 30 selected villages were enrolled. Indoor 24-h NO2 and SO2 samples were collected in each household over two consecutive days. Compared to smoky coal, smokeless coal use was associated with higher NO2 concentrations [geometric mean (GM) = 132 µg/m(3) for smokeless coal and 111 µg/m(3) for smoky coal, P = 0.065] and SO2 [limit of detection = 24 µg/m(3) ; percentage detected (%Detect) = 86% for smokeless coal and 40% for smoky coal, P < 0.001]. Among smoky coal users, significant variation of NO2 and SO2 air concentrations was observed across different stove designs and smoky coal sources in both counties. Model construction indicated that the measurements of both pollutants were influenced by stove design. This exposure assessment study has identified high levels of NO2 and SO2 as a result of burning solid fuels for cooking and heating.

Outdoor, indoor, and personal black carbon exposure from cookstoves burning solid fuels.

Black carbon (BC) emissions from solid fuel combustion are associated with increased morbidity and mortality and are important drivers of climate change. We studied BC measurements, approximated by particulate matter (PM2.5 ) absorbance, in rural Yunnan province, China, whose residents use a variety of solid fuels for cooking and heating including bituminous and anthracite coal, and wood. Measurements were taken over two consecutive 24-h periods from 163 households in 30 villages. PM2.5 absorbance (PMabs ) was measured using an EEL 043 Smoke Stain Reflectometer. PMabs measurements were higher in wood burning households (16.3 × 10(-5) /m) than bituminous and anthracite coal households (12 and 5.1 × 10(-5) /m, respectively). Among bituminous coal users, measurements varied by a factor of two depending on the coal source. Portable stoves (which are lit outdoors and brought indoors for use) were associated with reduced PMabs levels, but no other impact of stove design was observed. Outdoor measurements were positively correlated with and approximately half the level of indoor measurements (r = 0.49, P < 0.01). Measurements of BC (as approximated by PMabs ) in this population are modulated by fuel type and source. This provides valuable insight into potential morbidity, mortality, and climate change contributions of domestic usage of solid fuels.

Hepcidin levels in diabetes mellitus and polycystic ovary syndrome.

AIM: Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load. METHODS: Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16). RESULTS: Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = -0.59, P < 0.05). CONCLUSION: Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states.

Community attitudes towards leprosy affected persons in Pokhara municipality of western Nepal.

BACKGROUND: Stigma is a social process of interpretation of an attribute. Leprosy has been seen as the epitome of stigmatization. The psychosocial impact a person has to bear in a society after the diagnosis weighs heavier than the physical afflictions it causes, which does not get cured with the mere medical treatment. There are various factors which construct the perception of stigma in both leprosy affected persons and unaffected persons. The main purpose of this study was to determine the level of perceived stigma and the risk factors contributing to it among community people living in ward 15, Pokhara municipality. METHODS: Cross-sectional descriptive study among 281 community people above the age of 18 years was conducted. Two sets of questionnaire form with additional Explanatory Model Interview Catalogue (EMIC) for each individual were used. RESULTS: Among 281 community people, the median score of perceived stigma was 12 while it ranged from 0-30. Ethnic groups, Brahmins, Dalits and minorities had highest perceived stigma score of 15 and above compared to the rest (p=0.001), community people living at the distance more than 2 km had highest perceived stigma score of 15 compared to those living closer to the hospital (p=0.019) and nuclear family had highest perceived stigma score of 15 compared to the joint family (p=0.014). People who lacked information on leprosy had higher score of perceived stigma compared to those who had information on leprosy (p=0.002).Similarly, those who perceived leprosy to be difficult to treat (p<0.001) and a severe disease (p<0.001) had highest score of perceived stigma. CONCLUSIONS: Stigma in leprosy was found highly associated with the lack of information about leprosy and their perception in treatment and disease severity. Stigma reduction strategies should focus on health education, targeting to alleviate their perception about the disease with their active participation.

Indoor air pollution and lung function growth among children in four Chinese cities.

UNLABELLED: Ambient air pollution has been associated with decreased growth in lung function among children; but little is known about the impact of indoor air pollution. We examined relationships between indoor air pollution metrics and lung function growth, among children (n = 3273) aged 6-13 years living in four Chinese cities. Lung function parameters (FVC and FEV(1) ) were measured twice a year. Questionnaires were used to determine home coal burning and ventilation practices. Generalized estimating equations were used to examine associations. Use of coal as a household fuel was associated with 16.5 ml/year lower (33%, P < 0.001) and 20.5 ml/year lower (39%, P < 0.001) growth in children's FEV(1) and FVC, respectively. FEV(1) growth was 10.2 ml/year higher (20%, P = 0.009), and FVC growth was 17.0 ml/year higher (33%, P < 0.001) among children who lived in houses with the presence of a ventilation device. Among children living in houses where coal was used as a fuel and no ventilation devices were present, adjusted FVC and FEV(1) growth, respectively, were 37% and 61% that of the average growth per year in the full cohort. This suggests that household coal use may cause deficits in lung function growth, while using ventilation devices may be protective of lung development. PRACTICAL IMPLICATIONS: Nearly 3.4 billion people use solid fuels in homes for cooking and/or heating. We report the following findings from a longitudinal study: (i) household coal use is significantly associated with reduction in children's lung function growth and (ii) the use of household ventilation devices is significantly associated with higher lung function growth, particularly among children living in households where coal is used as a fuel. These findings not only provide evidence that indoor coal use impairs children's lung development but also point to the importance of improving ventilation conditions in reducing harmful effects of indoor air pollution sources.

Differential effects of smoking on lung cancer mortality before and after household stove improvement in Xuanwei, China.

BACKGROUND: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China. METHODS: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement. RESULTS AND CONCLUSION: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Development of a novel immunoassay for the iron regulatory peptide hepcidin.

To date there have been few published immunoassays for the important iron regulator hepcidin. This study describes a novel competitive radioimmunoassay (RIA) for the bioactive hepcidin peptide. A rabbit anti-hepcidin polyclonal antibody was produced using synthetic hepcidin radiolabelled with 125I to produce a competitive RIA. Normal patient (n=47) samples were collected and assayed for hepcidin to determine a reference range. Other patient groups collected were ulcerative colitis (UC; n=40), iron deficiency anaemia (IDA; n=15), chronic kidney disease not requiring dialysis (CKD; n=45) and chronic kidney disease requiring dialysis (HCKD; n=94). Detection limit of the assay was determined as 0.6 ng/mL. Intra-assay precision was 5 ng/mL (7.2%) and 50 ng/mL (5.8%), interassay precision was 5 ng/mL (7.6%) and 50 ng/mL (6.7%). Analytical recovery was 98% (5 ng/mL), 94% (10 ng/mL) and 97% (50 ng/mL). The assay was linear up to 200 ng/mL. No demonstrable cross-reactivity with human insulin, glucagon I, angiotensinogen I, beta-defensin 1-4, alpha-defensin-1 and plectasin was observed. There was significant correlation (r=0.96, P < or = 0.0001) between the hepcidin RIA and an established hepcidin SELDI-TOF-MS method. Analysis of the normal human samples gave a reference range of 1.1-55 ng/mL for hepcidin. Further statistical evaluation revealed a significant difference between male and female hepcidin levels. There was significant correlation between hepcidin and ferritin in the control group (r=0.6, P < or = 0.0001). There was also a significant difference between the normal and disease groups (P < or = 0.0001). Healthy volunteers (n=10) showed a diurnal increase in plasma hepcidin at 4.00 pm compared to 8.00 am. A robust and optimised immunoassay for bioactive hepcidin has been produced and the patient sample results obtained further validates the important role of hepcidin in iron regulation, and will allow further investigation of this important peptide and its role in iron homeostasis.

Prevalence and determinants of diabetes among the elderly population in the Kathmandu Valley of Nepal.

Elderly populations are susceptible to many non-communicable diseases, including diabetes. Lack of awareness regarding disease status and risk factors increase complications and mortality. We conducted a cross-sectional community-based study of 1633 randomly selected participants aged 60 years and above in urban and rural areas in the Kathmandu Valley of Nepal. Study goals were: (i) to determine the prevalence of diabetes in elderly subjects as diagnosed prior to and during the study, and (ii) to identify and compare the determinants of diabetes as diagnosed prior to and during the study. A structured questionnaire was used to collect information regarding prevalence and potential determinants of diabetes diagnosed during and before the survey. Anthropometric measurements, blood pressure measurements and fasting blood sugar tests were also measured. Risk factor analysis was done using multinomial logistic regression; subjects with no diabetes constituted the reference group. We detected an overall diabetes prevalence of 25.9%, 17.3% diagnosed during the survey and 8.6% previously diagnosed. Age, disturbed sleep, and family history of hypertension were marginally significantly (p < 0.10) associated with diabetes diagnosed in the survey. In contrast, education, exercise, health perception, family history of hypertension, having a caretaker at night, receiving help from friends when seeking health care and mean waist circumference were significantly (p pounds 0.05) or marginally associated with diabetes detected before the survey. The high prevalence of diabetes in the elderly population studied, and the low level of prior diagnosis, identify an important public health problem. There is a need for improved screening of diabetes and improved health care and education in the elderly. There is also need for better understanding of risk factors associated with previously undiagnosed diabetes.

Respiratory responses to diverse indoor combustion air pollution sources.

UNLABELLED: Diverse indoor combustion sources contribute to the indoor air environment. To evaluate the effect of these sources on human respiratory health, we examined associations between respiratory conditions and household factors in the 2360 children's fathers (mean = 38.4 years old) and associations between lung function and household factors in 463 primary school children (mean = 8.3 years old) from Wuhan, China. Factor analysis developed new uncorrelated 'factor' variables. Unconditional logistic regression models or linear regression models, controlling for important covariates, estimated the respiratory health effects. Coal smoke derived from home heating ('heating coal smoke') was associated with high adult reporting of persistent cough, persistent phlegm, and wheeze. Cooking coal smoke was associated with physician-diagnosed adult asthma and decreased forced vital capacity (FVC), and forced expiratory volume at 1 s (FEV(1)) in children. The presence of any home cigarette smoker was associated with more reports of persistent cough, persistent phlegm, cough with phlegm, and bronchitis. Our study suggests that in Wuhan, there may be independent respiratory health effects of different indoor combustion sources and their exposure factors for these study populations. PRACTICAL IMPLICATIONS: We conclude that multiple indoor air pollution sources could have adverse respiratory health effects on both children and middle-aged men in the city of Wuhan, China. These results may have implications for the Wuhan local government, the Chinese government, or other related organizations in efforts on protecting public health through regulation of indoor air pollution from indoor combustion sources.

High success rate of TB treatment among Bhutanese refugees in Nepal.

SETTING: Camps for refugees from Bhutan in south-east Nepal. OBJECTIVES: To evaluate the outcome of treatment of tuberculosis (TB) cases in the refugee camps. DESIGN: Cohort analysis of results of treatment of cases started on treatment from mid-July 1999 to mid-July 2004. RESULT: A total of 1214 patients with TB were notified in the programme. Among these, 631 (52%) were new smear-positive pulmonary tuberculosis (PTB) cases, 175 (14%) new smear-negative PTB cases, 290 (24%) new extra-pulmonary TB (EPTB) cases and 118 (10%) smear-positive retreatment cases. Treatment success was achieved in 1061 (94%). The proportion of new non-smear-positive cases who died on treatment was significantly higher than the corresponding figure for new smear-positive cases (RR 7.57, 95%CI 3.74-15.32 for new smear-negative and 4.22, 95%CI 2.08-8.55 for EPTB). CONCLUSION: High cure rates and low bacteriological failure rates can be achieved in refugee settings if there is close coordination and collaboration between the local health agencies and the National Tuberculosis Programme of the host country.

Surveillance of sexually transmitted diseases in general practice: a description of trends in the Royal College of General Practitioners Weekly Returns Service between 1994 and 2001.

This paper describes the incidence of sexually transmitted infections (STIs) recorded in the Weekly Returns Service (WRS) between 1994 and 2001. There were approximately 76,500 new diagnoses of STIs (7500 males, 71,000 females) and associated syndromes. Candidiasis was the commonest condition reported in males and females followed by pelvic inflammatory disease. The ratio of males to females was 7.1 for non-specific urethritis, and 9.1 and 2.1 for Reiter's syndrome and pediculosis pubis, respectively. The incidence of anogenital warts and genital herpes changed little over time. New diagnoses of genital herpes were higher in females than in males (ratio 2.8:1), whereas the mean annual incidence of genital warts was similar in males and females. The WRS provides an insight into the burden of STI diagnoses, and diagnoses related to STIs that are managed in general practice, and as such has the potential to make a substantial contribution to STI surveillance in England.

Surveillance of the bioterrorist threat: a primary care response.

Threats from bioterrorism are of national and international concern. We outline a system of disease surveillance covering a selection of diseases linked to potential bioterrorist threats, based on the weekly returns service of the Royal College of General Practitioners and covering a surveillance population of 650,000 in England and Wales. Practices record working diagnoses and the episode type (distinguishing new episodes of illness from ongoing consultations) on patients' computerised medical records. These are interrogated twice weekly by using automated routines. The registered population and persons consulting for each Read code (group of codes) are counted in sex and age specific groups and the data forwarded electronically to the Research Unit, where the results are consolidated by region (North, Central, South). Weekly incidence rates between October 2001 and September 2002 were compared with the weekly average over the past seven years for 13 selected conditions. Detailed data are presented for three conditions (asthma, infections of the skin, disorders of the peripheral nervous system). For asthma increased incidence was reported in weeks 31 and 32 of 2002, predominantly in the Central region. For the other two conditions no unusual peaks of incidence were observed in any region. Operational research based on disciplined recording of morbidity in general practice can deliver timely surveillance data on bioterrorist threats.

Predictors of parent-child language during novel task play: a comparison between typically developing children and individuals with Down syndrome.

Three questions were asked that explored the linguistic fine-tuning hypothesis and how parents might model language: (i) do parents significantly tune to their children's productive language or non-verbal cognition during play? (ii) is the level of the linguistic tuning different in the Down syndrome (DS) population compared to a typically developing (TD)-match group population? and (iii) do the two populations differ in requests for labels and the scaffolding responses to the requests? In an exploratory play condition, parents of children with DS used a mean length of utterance (MLU) significantly higher than the MLU used by the parents of younger TD children who were matched for MLU. Thus, the DS parents have a higher baseline MLU, but the non-significant correlations in the DS group do not support parental MLU tuning. There was evidence, however, for parental tuning to the children's lexicon using a number of different words when the DS children were at lower and average levels of receptive syntax and non-verbal cognition. In addition, DS and TD parents requested labels for novel toys with the same frequency, perhaps indicating that all groups of parents are still probing and building their children's lexicons. This is an important finding because it may help to explain why adolescents and young adults with DS have vocabulary comprehension skills greater than one would predict from measures of their production and non-verbal cognition.

Gender difference in the incidence of shingles.

We investigated age- and gender-specific incidence of shingles reported in a large sentinel practice network monitoring a defined population over the years 1994-2001. In total, 5915 male and 8617 female incident cases were studied. For each age group, we calculated the relative risk of females to males presenting with shingles. Incidence rates of chickenpox and herpes simplex were examined similarly. Shingles incidence was greater in females in each age group (except for 15-24 years). Relative risks (female to male) were greatest in age groups 45-64 years (1.48) and 0-14 years (1.43). There were no gender differences in the incidence of chickenpox except in the 15-24 years age group (female excess): for herpes simplex there were female excesses in all age groups. Gender-specific age-standardized incidence rates of shingles were calculated for each year and showed a consistent female excess in each of the 8 years (average annual excess 28%).

Language, cognition, and short-term memory in individuals with Down syndrome.

The developmentally emerging phenotype of language and cognition in individuals with Down syndrome is summarized on the basis of the project's prior work. Identified are a) the emerging divergence of expressive and receptive language, b) the emerging divergence of lexical and syntactic knowledge in each process, and c) the emerging divergence within cognitive skills of auditory short-term memory and visuospatial short-term memory from other visuospatial skills. Expressive syntax and auditory short-term memory are identified as areas of particular difficulty. Evidence for the continued acquisition of language skills in adolescence is presented. The role of the two components of working memory, auditory and visual, in language development is investigated in studies of narrative and longitudinal change in language skills. Predictors of individual differences during six years of language development are evaluated through hierarchical linear modelling. Chronological age, visuospatial short-term memory, and auditory-short term memory are identified as key predictors of performance at study entry, but not individual change over time, for expressive syntax. The same predictors account for variation in comprehension skill at study outset; and change over the six years can be predicted by chronological age and the change in visuospatial short-term memory skills.

Long-term ambient air pollution levels in four Chinese cities: inter-city and intra-city concentration gradients for epidemiological studies.

The field data collection of an air pollution epidemiologic study was carried out from 1993 to 1996 in four Chinese cities of Lanzhou, Chongqing, Wuhan, and Guangzhou. In each city, an urban district and a suburban district were selected. Ambient concentrations of total suspended particles (TSP), size-fractionated particulate matter including PM2.5, PM2.5-10, and PM10, sulfur dioxide (SO2), and oxides of nitrogen (NOx) were measured in these districts. The results indicate the presence of wide inter-city and intra-city gradients in long-term ambient levels of these measured pollutants. Across the eight districts, the 1993-1996 4-year means of TSP, SO2, and NOx ranged from 198 to 659 microg/m3, from 14.6 to 331 microg/m3, and from 31.5 to 239 microg/m3, respectively, and the 1995-1996 2-year means of PM2.5, PM2.5-10, and PM10 ranged from 51.5 to 142 microg/m3, from 29.2 to 107 microg/m3, and from 80.7 to 232 microg/m3, respectively. These pollution ranges substantially extended the upper end of the pollution ranges of previous air pollution epidemiologic studies conducted in North America and Europe. In each district, significant correlations among the measured pollutants were observed for daily concentrations. However, the gradient patterns in long-term means of different pollutants were different across the eight districts. (e.g., PM2.5-10 and TSP were highest in the Lanzhou urban district, PM2.5 and PM10 were highest in the Guangzhou urban district, SO2 was highest in the Chongqing urban district, and NOx was highest in the Guangzhou urban district). In general, seasonal variations were present in the ambient concentrations with high levels often occurring in winter months. The eight districts may be classified into four district clusters based on integrated levels of all measured pollutants. These features of the ambient air pollution have important implications for epidemiological studies and may provide unique opportunities to study exposure-effects relationships in the four Chinese cities.

p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells.

We have examined the effects of inhibition of the 26S proteasome in a murine mammary cell line, KIM-2 cells using the peptide aldehyde inhibitor MG132. These studies have demonstrated a clear requirement for proteasome function in cell viability. Induction of apoptosis was observed following MG132 treatment in KIM-2 cells and this death was shown to be dependent on the cell actively traversing the cell cycle. KIM-2 cells were generated using a temperature sensitive T-antigen (Tag) and studies at the permissive temperature (33 degrees C) have shown that a Tag binding protein was essential for this apoptotic response. Studies in two additional cell lines, HC11, which is a mammary epithelial cell line carrying mutant p53 alleles and p53 null ES cells suggest that p53 is actively required for the apoptosis induced as a consequence of proteasome inhibition. These results suggest a pivotal role for the 26S proteasome degradation pathway in progression through the cell cycle in proliferating cells.

A novel cell culture model for studying differentiation and apoptosis in the mouse mammary gland.

BACKGROUND: This paper describes the derivation and characterization of a novel, conditionally immortal mammary epithelial cell line named KIM-2. These cells were derived from mid-pregnant mammary glands of a mouse harbouring one to two copies of a transgene comprised of the ovine beta-lactoglobulin milk protein gene promoter, driving expression of a temperature-sensitive variant of simian virus-40 (SV40) large T antigen (T-Ag). RESULTS: KIM-2 cells have a characteristic luminal epithelial cell morphology and a stable, nontransformed phenotype at the semipermissive temperature of 37 degrees C. In contrast, at the permissive temperature of 33 degrees C the cells have an elongated spindle-like morphology and become transformed after prolonged culture. Differentiation of KIM-2 cells at 37 degrees C, in response to lactogenic hormones, results in the formation of polarized dome-like structures with tight junctions. This is accompanied by expression of the milk protein genes that encode beta-casein and whey acidic protein (WAP), and activation of the prolactin signalling molecule, signal transducer and activator of transcription (STAT)5. Fully differentiated KIM-2 cultures at 37 degrees C become dependent on lactogenic hormones for survival and undergo extensive apoptosis upon hormone withdrawal, as indicated by nuclear morphology and flow cytometric analysis. KIM-2 cells can be genetically modified by stable transfection and clonal lines isolated that retain the characteristics of untransfected cells. CONCLUSION: KIM-2 cells are a valuable addition, therefore, to currently available lines of mammary epithelial cells. Their capacity for extensive differentiation in the absence of exogenously added basement membrane, and ability to undergo apoptosis in response to physiological signals will provide an invaluable model system for the study of signal transduction pathways and transcriptional regulatory mechanisms that control differentiation and involution in the mammary gland.

The relationship between event representation and linguistic skill in narratives of children and adolescents with Down syndrome.

Children and adolescents with Down syndrome present with greater difficulty in expressive language than nonverbal cognitive domains. As narratives involve an understanding of the relationship(s) between events and their verbal expression, this divergence has implications for understanding narrative abilities in persons with Down syndrome. In this project, we investigated the relationship between event representation and linguistic expression in narratives of children and adolescents with Down syndrome (n = 31) and groups of typically developing children matched for mental age (n = 31), syntax comprehension (n = 28), or expressive language (n = 27). A short wordless film, the Pear Story (Chafe, 1980), was viewed individually by each participant and then each participant retold the story to an adult who (presumably) had not seen the film. Findings suggest a disparate relationship between linguistic expression and event representation in narratives of children and adolescents with Down syndrome. Participants with Down syndrome produced narratives that were significantly longer and more complex than the expressive-language-matched-group, with no differences observed in event structure when compared to the MA-matched group. Comparatively, use of linguistic devices and cohesion were poorer in the children and adolescents with Down syndrome than in the MA-matched children, with no differences observed in comparison to children matched for expressive language.

The role of Stat3 in apoptosis and mammary gland involution. Conditional deletion of Stat3.

STATs (signal transducer and activator of transcription) are a family of latent transcription factors which are activated in response to a variety of cytokines and growth factors. This family of signalling molecules have been implicated in growth, differentiation, survival and apoptosis. In this article, we will review work which highlights the role of individual STAT factors in mammary gland and demonstrate the value of genetically modified mice in defining the function of STAT3. Involution of the mouse mammary gland is characterised by extensive apoptosis of the epithelial cells and the activation of STAT3. STATs 3 and 5 have reciprocal patterns of activation throughout a mammary developmental cycle suggesting that STAT5 may be a survival factor and STAT3 a death factor for differentiated mammary epithelium. To clarify the role of STAT3 in mammary epithelial apoptosis, we have generated a conditional knockout using the lox/Cre recombination system. Mammary glands from crosses of transgenic mice expressing Cre recombinase under the control of the beta-lactoglobulin milk protein gene promoter with mice harbouring one floxed STAT3 allele and one null STAT3 allele, showed a decrease in epithelial apoptosis and a dramatic delay of the involution process upon forced weaning. This was accompanied by precocious activation of STAT1 and increases in p53 and p21 levels--these may act as a compensatory mechanism for initiating the eventual involution which occurs in STAT3 null mammary glands. This demonstrates for the first time the importance of STAT factors in signalling the initiation of physiological apoptosis in vivo and highlights the utility of the lox/Cre system for addressing the function of genes, which have an embryonic lethal phenotype, specifically in mammary gland.