It starts from the womb: maximizing bone health.

The foundation of bone health is established in utero. Bone accrual starts from the developing fetus and continues throughout childhood and adolescence. This process is crucial to achieve peak bone mass. Understanding factors that influence bone accrual before attainment of peak bone mass is thus critical to improve bone health and prevent osteoporosis, thereby reducing the burden of osteoporotic fractures in older women. In this review, we broadly outline factors influencing peak bone mass from pregnancy to infancy, childhood and adolescence with potential diseases and medications that may affect the optimum trajectory to maximizing bone health. It is estimated that a 10% increase in peak bone mass will delay the onset of osteoporosis by 13 years in a woman.

A pilot screening study for low bone mass in Singaporean women using years since menopause and BMI.

OBJECTIVE: Current risk assessment tools for osteoporosis have inconsistent performance across different cohorts, making them difficult for clinical practice. This study aimed to evaluate a simple screening index comprising years since menopause (YSM) and body mass index (BMI) that identifies postmenopausal Singaporean women with a greater likelihood of low bone mass. METHODS: The study used data from 188 treatment-naïve postmenopausal women. The associations between low bone mass and different demographic variables, including age, YSM and BMI, were assessed using multivariable logistic regression. Diagnostic performance of the calculated screening index was compared to the Osteoporosis Self-Assessment Tool for Asians (OSTA) and the Fracture Risk Assessment Tool (FRAX®). RESULTS: YSM and BMI were significantly associated with low bone mass. The area under the receiver operating characteristic curves was 0.803 for the screening index, 0.759 for the OSTA, 0.683 for the FRAX® (major osteoporotic fracture probability [MOFP]) and 0.647 for the FRAX® (hip fracture probability [HFP]). Non-parametric Spearman's correlation between the screening index and the other models was 0.857 with the OSTA score, 0.694 with the FRAX® (HFP) and 0.565 with the FRAX® (MOFP) (p < 0.0005). CONCLUSIONS: The diagnostic performance of the screening index comprising YSM and BMI was equivalent to the OSTA and the FRAX®. A risk chart was developed for clinicians to identify and recommend subjects for a further dual-energy X-ray absorptiometry scan. Validation of this model in larger and more diverse cohorts is required.

The risk factors for complications and survival outcomes of Klebsiella pneumoniae Bacteraemia in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia.

INTRODUCTION: Mortality of Klebsiella pneumoniae (K. pneumoniae) bacteraemia was reported to be on the rise globally. The 30-day mortality rate of K. pneumoniae bacteraemia ranges from 16% to 55% in Beijing, Shanghai, and Taiwan. However, there is a lack of research on the survival outcomes of K. pneumoniae bacteraemia in Malaysia. The objectives of this study were to determine the poor prognostic factors and predictors of 14-day in-hospital mortality from K. pneumoniae bacteraemia. METHODS: This was a retrospective cohort study of patients with K. pneumoniae bacteraemia in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM). We included adult patients with blood cultures positive for K. pneumoniae between 1 January 2016 and 31 December 2019. Those with polymicrobial bacteraemia were excluded. Medical records were reviewed to obtain the sociodemographic data, gender, underlying comorbidities, invasive procedures at presentation, sources of bacteraemia, and whether appropriate empirical and definitive antibiotics was given on time. Data regarding complications of K. pneumoniae bacteraemia, including liver abscess, endopthalmitis, septic shock, Quick Pitt (qPitt) bacteraemia score defined as hypothermia, hypotension, respiratory failure, cardiac arrest, and altered mental status and stay in intensive care unit (ICU) were also recorded. The main outcome measure used was the survival in 14 days. Summary of statistical analysis was done. RESULTS: A total of 260 patients with K. pneumoniae bacteraemia were included. All patients received appropriate empirical and definitive antibiotics within 24 h of the time that the sample for index blood cultures was obtained. Respiratory infection, septic shock, qPitt bacteraemia score ≥2, solid organ malignancy, stay in ICU, central venous line insertion at presentation, urinary catheterisation at presentation, and in-patient mechanical ventilation were identified as independent predictors of mortality in K. pneumoniae bacteraemia. The rate of complications such as liver abscess, endophthalmitis, ICU admission, and septic shock was not significantly different between survivors and non-survivors. The 14-day in-hospital mortality rate was 12.3%. The median length of hospitalisation was 11 days (IQR 6 - 19) . The predictors of poor prognosis for 14 days in-hospital mortality for K. pneumoniae bacteraemia were as follows: qPitt bacteraemia score ≥2, central venous line insertion, indwelling urinary catheter at presentation, and in-patient mechanical ventilation. Timing from K. pneumoniae bacteraemia event to death among those qPitt bacteraemia scores ≥2 was only for 9 days or less. CONCLUSIONS: The 14-day in-hospital mortality of patients with K. pneumoniae bacteraemia in our setting was low. The qPitt bacteraemia score ≥2 was the strongest predictor of poor prognosis for 14-day in-hospital mortality in patients with K. pneumoniae bacteraemia. The qPitt bacteraemia score should be proposed to be used as a bedside screening tool for gram negative bacteraemia in our daily clinical practice, which is also useful for predicting mortality in critically ill patients.

Association between demographics and resilience - a cross-sectional study among nurses in Singapore.

AIM: To give an overview of the level of resilience among nurses in Singapore and to examine associations between various demographics variables and resilience level. BACKGROUND: The World Health Organization reported a global needs-based shortage of over 9 million nurses and midwives in 2013. Building resilience among nurses has been postulated as one of the ways to support and retain nurses in the profession. METHOD: A self-reported questionnaire consisting of questions on demographics and the Connor-Davidson Resilience Scale CD-RISC 10 was used. RESULTS: Univariate analysis identified marital status, age group, years of experience in nursing, highest education qualification and job grade to have significant associations with resilience. During multivariate analysis, only marital status, age group, highest educational qualification and job grade remained significant. A strong association was found between highest educational qualification and resilience level; nurses with bachelor's or postgraduate degree were about three times more likely than nurses with only a general nursing certificate to be of moderate/high resilience. CONCLUSION: The experience of life events (as exemplified by marital status, age and working experience) was associated with higher resilience levels. IMPLICATIONS FOR NURSING POLICY: There is a need for healthcare organizations and nurse leaders to develop programmes focusing on building resilience among younger and less experienced nurses. Nurses should also be supported in their pursuits for higher education, which will in turn lead to higher resilience, and consequently, retention of nurses within the profession and institution.

Challenges faced by older nurses in Singapore: a mixed methods study.

BACKGROUND: In Singapore, employees aged 62-65 can continue to be employed if they meet the re-employment eligibility criteria. This policy, coupled with an ageing workforce, calls for age-friendly initiatives, specific to work-related challenges faced by older nurses. AIM: To determine work-related challenges faced by older nurses. METHODS: A mixed method sequential explanatory study was conducted with nurses, aged 50 and above, working in a healthcare cluster in Singapore. In the quantitative phase, a questionnaire was administered to 534 nurses to elicit work-related challenges, then in-depth interviews with 30 nurses were carried out to help explain why certain tasks and work circumstances became harder. RESULTS: Results of the survey indicated that the top three challenges were coping with changes, working with computers and reading labels. Place of work, salary range, gender and race were significantly associated with different work-related challenges. Five themes emerged from the qualitative data: physical demands of work and workload, new technology, need for further education, working with younger nurses and in intercultural teams, and changing public expectations and professional image. DISCUSSION AND CONCLUSION: The study supports the current literature on the challenges older nurses face with technological advancement. However, older nurses in our study reported less aches and pain as compared to that reported elsewhere. There is a need for specific strategies that will address changes in work processes and environment in order to retain older nurses. IMPLICATIONS FOR NURSING AND NURSING POLICY: When devising age-friendly work improvement initiatives, it is important for nurse leaders to factor in the needs of nurses working in different care environments, who are of different ranks, or are from different ethnic backgrounds.

Assessment of the level of knowledge of colorectal cancer among public at outpatient clinics in Serdang Hospital: a survey based study.

OBJECTIVES: Colorectal cancer (CRC) is one of the most common gastrointestinal cancers in the world. In the Asia- Pacific region, it is the fastest emerging gastrointestinal cancer. Level of awareness on CRC warning signs and risk factors in the rural population of Malaysia is reported of very low. The aim of this study was to assess the level of knowledge of CRC among the public at medical outpatient clinics in Serdang Hospital. The association between sociodemographic factors with level of knowledge among the respondents was further studied. STUDY DESIGN: A study was conducted among the non-CRC patients' relatives accompanying their relatives to the medical outpatient clinics in Serdang Hospital from 1st April to 31st August 2016. The study was carried out with cluster sampling method. METHODS: The respondents were assessed using validated and modified Cancer Awareness Measures (CAM) questionnaire consists of three parts which are knowledge on warning signs, knowledge on risk factors and sociodemographic factors. All data were analysed using IBM SPSS Statistics 21.0. RESULTS: Altogether 308 subjects completed the questionnaires. It was shown high percentage of good knowledge for warning signs and risk factors of CRC among the respondents. A significant association between age groups and level of income with level of knowledge on warning signs was observed. CONCLUSIONS: The level of knowledge of CRC among the general public in Serdang Hospital was sufficient. The respondents with higher income or younger age had higher level of knowledge regarding CRC.

Increased risk of strontium ranelate-related SJS/TEN is associated with HLA.

UNLABELLED: Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN. INTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant. METHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles. RESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n = 76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n = 5). The majority of the accrued samples were of Han Chinese descent: controls (n = 72) and cases (n = 4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p = 0.002) and HLA-B*58:01 (p = 0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles. CONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate.

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BACKGROUND: Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. PATIENTS AND METHODS: Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. RESULTS: Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1ß was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1ß and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). CONCLUSIONS: While elevated concentrations of IL-6 and IL-1ß were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Heterogeneous photo-Fenton reaction on hematite (α-Fe2O3){104}, {113} and {001} surface facets.

The exposed surface facets play an important role in determining the catalytic performance of nanostructured materials. In this study, we report the synthesis of hematite nanoparticles with three varying morphologies with exposure of well-controlled {104}, {113} and {001} surfaces. The better shape control of hematite particles has provided a direct correlation between the surface facets and the photocatalytic performance. The catalytic photodegradation of MB using hematite nanoparticles reveals that the reaction follows the heterogeneous photo-Fenton process under visible light irradiation. The catalytic performance of hematite surface facets follows the order of {113} > {104} > {001}. Density functional theory (DFT) calculations were conducted to demonstrate the atomic surface structures and the corresponding charge distribution. The results indicate that the catalytic activity depends on surface atom arrangements as well as the number and the type of surface terminated hydroxyl groups bonding to underlying Fe atoms, where low valence states of Fe on {104} and {113} planes have the highest probability to be oxidized by H2O2 and the concurrently generated Fe((3+x)+) sites are more electronegative to accept electrons from activated dye molecules. The findings are of fundamental importance to understand the surface-dependence of photocatalytic properties, thus shedding new light on the catalytic application of hematite particles.

Use of emollients in atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder that has strong financial and psychosocial impacts. Its pathogenesis is related to increased transepidermal water loss due to a defective skin epidermal barrier. Emollients serve as first-line therapy during both acute flares and remission. However, their use is poorly characterized, posing therapeutic challenges to clinicians and patients. In this article, we review available evidence to provide recommendations, aiming to standardize and optimize the use of emollients in AD. Literature search was performed using Pubmed and Google. All articles were retrieved using Pubmed. Recommendations were graded based on the British Medical Journal's Grading of Recommendations Assessment, Development and Evaluation system and the American Academy of Family Physicians' Strength of Recommendation Taxonomy. Emollients should be applied post-bathing. However, the need for immediate application is debatable. The optimal frequency for application is still undetermined, but multiple applications daily are encouraged. Ideally, a balance should be achieved between patient's compliance and clinical efficacy. Emollients hold the potential to act as steroid-sparing agents, but more well-designed studies are pertinent for a definite conclusion. At present, it is recommended that 250-500 g of emollients be applied every week. Finally, primary prevention of AD by regular application of emollients in high-risk infants cannot yet be recommended.

Isolation, screening, and identification of potential cellulolytic and xylanolytic producers for biodegradation of untreated oil palm trunk and its application in saccharification of lemongrass leaves.

This study presents the isolation and screening of fungi with excellent ability to degrade untreated oil palm trunk (OPT) in a solid-state fermentation system (SSF). Qualitative assay of cellulases and xylanase indicates notable secretion of both enzymes by 12 fungal strains from a laboratory collection and 5 strains isolated from a contaminated wooden board. High production of these enzymes was subsequently quantified in OPT in SSF. Aspergillus fumigates SK1 isolated from cow dung gives the highest xylanolytic activity (648.448 U g(-1)), generally high cellulolytic activities (CMCase: 48.006, FPase: 6.860, beta-glucosidase: 16.328 U g(-1)) and moderate lignin peroxidase activity (4.820 U/g), and highest xylanolytic activity. The xylanase encoding gene of Aspergillus fumigates SK1 was screened using polymerase chain reaction by a pair of degenerate primers. Through multiple alignment of the SK1 strain's xylanase nucleotide sequences with other published xylanases, it was confirmed that the gene belonged to the xylanase glycoside hydrolase family 11 (GH11) with a protein size of 24.49 kD. Saccharification of lemongrass leaves using crude cellulases and xylanase gives the maximum reducing sugars production of 6.84 g/L with glucose as the major end product and traces of phenylpropanic compounds (vanillic acid, p-coumaric acid, and ferulic acid).

Amperometric nitric oxide sensor based on nanoporous platinum phthalocyanine modified electrodes.

This article describes the fabrication of electropolymerized Metallo 4', 4″, 4‴, 4'''' tetra-amine phthalocyanine (poly-MTAPc) modified electrodes for the detection of nitric oxide (NO) in phosphate-buffered saline (PBS) at pH 7.4. A two-step synthetic protocol using a laboratory microwave reactor was adopted to provide three MTAPc complexes bearing different metal centers (M = Cu(2+): CuTAPc, M = Zn(2+): ZnTAPc, and M = Pt(2+): PtTAPc). The MTAPc complexes and the intermediates were characterized by MALDI-TOF mass spectrometry, UV-vis spectroscopy, (1)H NMR spectroscopy, and elemental analysis. The MTAPc products were separately electropolymerized either onto a glassy carbon (GC) electrode as a thin-film or within the pores of Anodisc nanoporous alumina membrane as a densely packed array of poly-MTAPc nanotubes to produce two electrode systems. In the latter system, the surface area enhancement provided by the nanotube-arrayed morphology of the poly-MTAPc enabled a high faradaic (signal) to capacitative (background) current during NO electro-oxidation. Amperometric detection of NO using these two electrode systems shows that the sensitivity and linear ranges were insensitive to the metal centers (M = Cu(2+), Zn(2+), and Pt(2+)) of the poly-MTAPc material.

Herbal Ingestion During Pregnancy and Post-Partum Period is A Cause For Concern.

The potential harms of herbs to the pregnant mothers and their foetuses as well as the effect of herbs taken by nursing mothers on their babies remain largely unknown. Common perception is that herbal medicines ingestion during pregnancy and confinement period is a common practice among multi-racial Malaysian mothers. The purpose of this study was to explore the usage of herbal medicines during pregnancy and post-partum period among mothers who gave birth at a tertiary hospital in a metropolitan city of Malaysia. This cross sectional study was conducted between October and December 2010. The subjects were interviewed twice after giving birth: before hospital discharge and 6 to 8 weeks later. A total of 323 mothers were recruited for this study. The prevalence of herbs ingestion during pregnancy was 13.9%, with half of the users consuming it during the first trimester. A total of 163 (52.9%) mothers ingested herbs during the post-partum period. Significantly more Chinese (p=0.01) and Malay (p=0.04) mothers ingested herbs during pregnancy and post-partum period, respectively. Infants of mothers who ingested herbs had a higher rate of neonatal jaundice compared to infants of mothers who did not ingest herbs during the post-partum period (P=0.001).

Western Australian adolescent emotional wellbeing during the COVID-19 pandemic in 2020.

BACKGROUND: The impacts of the COVID-19 pandemic have been vast and are not limited to physical health. Many adolescents have experienced disruptions to daily life, including changes in their school routine and family's financial or emotional security, potentially impacting their emotional wellbeing. In low COVID-19 prevalence settings, the impact of isolation has been mitigated for most young people through continued face-to-face schooling, yet there may still be significant impacts on their wellbeing that could be attributed to the pandemic. METHODS: We report on data from 32,849 surveys from Year 7-12 students in 40 schools over two 2020 survey cycles (June/July: 19,240; October: 13,609), drawn from a study of 79 primary and secondary schools across Western Australia, Australia. The Child Health Utility Index (CHU9D) was used to measure difficulties and distress in responding secondary school students only. Using comparable Australian data collected six years prior to the pandemic, the CHU9D was calibrated against the Kessler-10 to establish a reliable threshold for CHU9D-rated distress. RESULTS: Compared to 14% of responding 12-18-year-olds in 2013/2014, in both 2020 survey cycles almost 40% of secondary students returned a CHU9D score above a threshold indicative of elevated difficulties and distress. Student distress increased significantly between June and October 2020. Female students, those in older Grades, those with few friendships or perceived poor quality friendships, and those with poor connectedness to school were more likely to score above the threshold. CONCLUSIONS: In a large dataset collected during the first year of the COVID-19 pandemic, the proportion of secondary school students with scores indicative of difficulties and distress was substantially higher than a 2013/2014 benchmark, and distress increased as the pandemic progressed, despite the low local prevalence of COVID-19. This may indicate a general decline in social and emotional wellbeing exacerbated by the events of the pandemic. TRIAL REGISTRATION: ANZCTRN (ACTRN12620000922976). Retrospectively registered 17/08/2020. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380429&isReview=true .

Functional gamma chain-associated T cell receptors on cerebrospinal fluid-derived natural killer-like T cell clones.

We have derived 33 independent T cell clones from the cerebrospinal fluid (CSF) of a patient with subacute sclerosing panencephalitis using a single T cell cloning method. 6% (2 of 33) of these clones express the T cell receptor gamma (TCR-gamma) protein and are called CSF TCR-gamma clones. Phenotypic analyses of the CSF TCR-gamma clones indicate that they are WT-31-, CD3+, CD4-, and CD8-. The TCR-gamma protein exists on the cell surface as part of an 85-kD disulphide-linked dimer noncovalently associated with the CD3 polypeptides. The CSF TCR-gamma clones have NK-like activity that can be inhibited by anti-CD3 mAbs. Both CSF TCR-gamma clones proliferated in response to anti-CD3 mAbs coupled to Sepharose beads and/or IL-2. Furthermore, stimulation of one of these clones with anti-CD3 mAbs results in a rapid rise in intracellular calcium. These data suggest that T cells bearing the CD3-TCR-gamma protein complex are functional and play a role in the human immune response.

bcl-2 transgene expression inhibits apoptosis in the germinal center and reveals differences in the selection of memory B cells and bone marrow antibody-forming cells.

Immunization with T cell-dependent antigens generates long-lived memory B cells and antibody-forming cells (AFCs). Both populations originate in germinal centers and, predominantly, produce antibodies with high affinity for antigen. The means by which germinal center B cells are recruited into these populations remains unclear. We have examined affinity maturation of antigen-specific B cells in mice expressing the cell death inhibitor bcl-2 as a transgene. Such mice had reduced apoptosis in germinal centers and an excessive number of memory B cells with a low frequency of V gene somatic mutation, including those mutations encoding amino acid exchanges known to enhance affinity. Despite the frequency of AFCs being increased in bcl-2-transgenic mice, the fraction secreting high-affinity antibody in the bone marrow at day 42 remained unchanged compared with controls. The inability of BCL-2 to alter selection of bone marrow AFCs is consistent with these cells being selected within the germinal center on the basis of their affinity being above some threshold rather than their survival being due to a selective competition for an antigen-based signal. Continuous competition for antigen does, however, explain formation of the memory compartment.

Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis.

Mammalian hairy and Enhancer of split homolog 1 (HES1), a basic helix-loop-helix factor gene, is expressed in retinal progenitor cells, and its expression decreases as differentiation proceeds. Retinal progenitor cells infected with HES1-transducing retrovirus did not differentiate into mature retinal cells, suggesting that persistent expression of HES1 blocks retinal development. In contrast, in the retina of HES1-null mutant mice, differentiation was accelerated, and rod and horizontal cells appeared prematurely and formed abnormal rosette-like structures. Lens and cornea development was also severely disturbed. Furthermore, in the mutant retina, bipolar cells extensively died, and finally disappeared. These studies provide evidence that HES1 regulates differentiation of retinal neurons and is essential for eye morphogenesis.

Distinct regulators control the expression of the mid-hindbrain organizer signal FGF8.

Local expression of FGF8 at the mid/hindbrain boundary (MHB) governs the development of multiple neurons and support cells. Here we show that the paired-domain protein Pax2 is necessary and sufficient for the induction of FGF8 in part by regulating the expression of Pax5&8. A network of transcription and secreted factors, including En1, Otx2, Gbx2, Grg4 and Wnt1&4, that is established independently of Pax2, further refines the expression domain and level of FGF8 at the MHB through opposing effects on Pax2 activity. Our results indicate that the expression of local organizing factors is controlled by combinatorial interaction between inductive and modulatory factors.

Acute leukemia expressing the gamma gene product of the putative second T cell receptor.

Early thymus-derived lymphocytes bearing the T gamma gene product in association with the CD3(T3) complex have recently been described. We report a unique case of human acute lymphoblastic leukemia with a CD2+, CD3+, CD4-, CD5+, CD7+, CD8-, WT31- phenotype. These cells were found to have T gamma gene rearrangement and T gamma transcripts in absence of T alpha or T beta rearrangement or transcripts. Immunoprecipitation studies with anti-CD3 antibodies showed a 43-kD protein associated with T3; this 43-kD protein is also precipitated with antiserum raised against synthetic peptides representing the constant region of the putative T gamma protein.

Hepatocyte nuclear factor 3beta (Foxa2) is dispensable for maintaining the differentiated state of the adult hepatocyte.

Liver-specific gene expression is controlled by a heterogeneous group of hepatocyte-enriched transcription factors. One of these, the winged helix transcription factor hepatocyte nuclear factor 3beta (HNF3beta or Foxa2) is essential for multiple stages of embryonic development. Recently, HNF3beta has been shown to be an important regulator of other hepatocyte-enriched transcription factors as well as the expression of liver-specific structural genes. We have addressed the role of HNF3beta in maintenance of the hepatocyte phenotype by inactivation of HNF3beta in the liver. Remarkably, adult mice lacking HNF3beta expression specifically in hepatocytes are viable, with histologically normal livers and normal liver function. Moreover, analysis of >8,000 mRNAs by array hybridization revealed that lack of HNF3beta affects the expression of only very few genes. Based on earlier work it appears that HNF3beta plays a critical role in early liver development; however, our studies demonstrate that HNF3beta is not required for maintenance of the adult hepatocyte or for normal liver function. This is the first example of such functional dichotomy for a tissue specification transcription factor.