Optimising the effectiveness of diabetes education in an East Asian population.

AIM: To explore the collective patterns of learning behaviours and preferences of Chinese people during diabetes education. The study was carried out across three countries and aimed to identify strategies that could be used to tailor diabetes education to Chinese people. METHODS: A case study approach was undertaken in three countries (Australia, China and Singapore) using participant observations and qualitative interviews. Purposive sampling was used to select field sites before a snowball technique was employed to identify relevant interviewees. Thematic analysis with pattern matching was used for data analysis. RESULTS: A total of 39 participant observations and 22 interviews were conducted. Chinese people with diabetes were observed seeking advice and recommendations from health professionals. When told clearly what to do, they strived for full compliance. They tended to be submissive during diabetes education and were not likely to raise concerns, negotiate or participate in making medical decisions. They appeared to prefer prescriptive concrete instructions rather than more flexible conceptual education and to believe that behavioural change should be achieved by individual willpower and determination, resulting in an 'all-or-nothing' approach. Regular repeated information sessions were reported to establish rapport and trust. CONCLUSIONS: For diabetes education to be culturally modified for Chinese people, there is a need to consider their unique philosophies and behaviours during education to support lifestyle changes. Building trust from the early stages of education was achieved by encouraging rapport through the provision of clear and precise instructions. This should be done before engaging in an open discussion of implementation strategies. Once the trust is built, healthy behaviour change may follow.

Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome.

BACKGROUND: Pseudolymphoma syndrome (PLS) is relatively rare but can lead to death if there are extensive skin lesions, severe hepatitis, agranulocytosis and neutropenia. PLS may also give rise to harmful effects if misdiagnosed as malignant lymphoma and patients with PLS are treated unnecessarily with chemotherapy, because it may mimic histologically other lymphomas, including mycosis fungoides (MF). OBJECTIVES: To examine the clinicopathological and genotypic features of anticonvulsant-induced PLS. Patients and methods We retrospectively reviewed clinical, laboratory and histological findings for eight cases of anticonvulsant-induced PLS, and performed T-cell receptor gene rearrangement using polymerase chain reaction with paraffin-embedded specimens from each case. RESULTS: The causative agents were carbamazepine (four cases), phenytoin (two cases), phenobarbital (one case) and valproic acid (one case). A cross-reaction between phenobarbital and phenytoin was observed in one case. The duration from the start of anticonvulsant therapy to skin eruption was 3-24 weeks (mean 7 weeks). The skin lesions were generalized maculopapular eruptions in all cases, including one case accompanied by vesiculopustular lesions. The frequencies of the associated features were as follows: facial oedema (88%), fever (75%), lymphadenopathy (63%), and hepatomegaly (25%). Laboratory findings revealed leukocytosis, atypical lymphocytes, eosinophilia, monocytosis, neutrophilia, lymphocytosis and abnormal liver function. Histopathologically, there was similarity between PLS and MF in that epidermotrophism of atypical lymphocytes (100%) and Pautrier's microabscess-like structures (38%) were observed. However, PLS has some differences from MF that include moderate to marked spongiosis (75%), necrotic keratinocytes (63%), and infiltration of eosinophils (25%) in the epidermis and, in the dermis, papillary dermal oedema (100%), extravasated erythrocytes (100%), lymphocytes within the dermis larger than those within the epidermis (63%), and infiltration of various inflammatory cells including neutrophils (50%). Genotypic analysis demonstrated a rearrangement of the T-cell receptor-gamma gene in one of eight cases studied. There were no deaths and all cases were improved at 2-9 weeks (mean 6 weeks), after the cessation of causative agents, systemic and topical corticosteroid therapy, and symptomatic therapy. There were no significant differences in clinical, laboratory and histological findings between the causative agents. CONCLUSIONS: PLS may show histopathological findings similar to MF and take a prolonged course even after the cessation of causative agents. Thus, a clear understanding and diagnosis of this disease is considered to have an important effect on treatment and prognosis.

Mycosis fungoides presenting as Ofuji's papuloerythroderma.

We report three patients presented with clinical features of Ofuji's papuloerythroderma (pruritic erythematous papules and extensive erythema sparing all skin folds), however, showing histopathological findings of mycosis fungoides (Pautrier's microabscess, haloed lymphocytes, disproportionate epidermotropism, and wiry collagen bundles). One case was associated with plaque stage of mycosis fungoides and follicular mucinosis. T-cell receptor (TCR) gene rearrangement analysis in the lesional skin tissue demonstrated rearrangement of the gamma chain in all cases. HTLV-1 serology was negative for two patients who conducted HTLV-1 test. We think that Ofuji's papuloerythroderma might be a variant of early mycosis fungoides rather than secondary skin manifestations to certain cutaneous inflammatory diseases.

p53 and its homologues, p63 and p73, induce a replicative senescence through inactivation of NF-Y transcription factor.

Recent studies have identified two p53 homologues, p63 and p73. They activate p53-responsive promoters and induce apoptosis when overexpressed in certain human tumors. Here, we report that p63, like p53 and p73, induces replicative senescence when expressed in a tetracycline-regulated manner in EJ cells lacking a functional p53. In addition to transcription activation of p53-responsive genes, we found that p63 and p73 repress transcription of the cdk1 and cyclin B genes, both of which are irreversibly repressed in senescent human fibroblast. In transient transfection assay, p63 and p73 repress the cdk1 promoter regardless of the presence of a dominant negative mutant form of p53. Furthermore, we found that DNA binding activity of NF-Y transcription factor, which is essential for transcription of the cdk1 and cyclin B genes and inactivated in senescent fibroblast, is significantly decreased by expression of either of p53, p63, or p73. Since NF-Y binds to many promoters besides the cdk1 and cyclin B promoters, inactivation of NF-Y by p53 family genes may be a general mechanism for transcription repression in replicative senescence.

Insulin Induction of SOCS-2 and SOCS-3 mRNA expression in C2C12 Skeletal Muscle Cells Is Mediated by Stat5*.

Previously, by a yeast 2-hybrid screen, we identified signal transducer and activator of transcription 5b (Stat5b) as a substrate of the insulin receptor (IR). We demonstrated that refeeding of fasted mice leads to rapid activation of Stat5 proteins in liver, skeletal muscle, and fat, suggesting that Stat5b is a physiological target of insulin. Here, we show that injection of glucose or insulin into fasted mice leads to robust activation of both Stat5a and Stat5b in skeletal muscle. In C2C12 myotubes, we find that insulin stimulates tyrosine phosphorylation of Stat5a and Stat5b by 3-5-fold. This degree of Stat5 activation in vitro is significantly lower than what we observe in vivo and inversely correlates with IRS-1/2 levels. We can recapitulate robust insulin activation of Stat5 in C2C12 cells by stable overexpression of the human IR (hIR). To identify insulin-activated genes that are Stat5 targets, we also overexpressed an IR mutant (LA-hIR) that signals normally for mitogen-activated protein kinase- and phosphatidylinositol 3-kinase-dependent pathways but is deficient in Stat5 signaling in response to insulin. We demonstrate that insulin induces the expression of SOCS-2 mRNA in the wild type hIR but not in the LA-hIR-overexpressing cells. The induction of SOCS-3 by insulin is reduced but not lost in the LA-hIR cells. Therefore, our results suggest that insulin induction of SOCS-2, and in part SOCS-3 mRNA expression, is mediated by Stat5 and can be independent of mitogen-activated protein kinase and phosphatidylinositol 3-kinase-signaling pathways.

Shape from focus using multilayer feedforward neural networks.

The conventional shape-from-focus (SFF) methods have inaccuracies because of piecewise constant approximation of the focused image surface (FIS). We propose a scheme for SFF based on representation of three-dimensional (3-D) FIS in terms of neural network weights. The neural networks are trained to learn the shape of the FIS that maximizes the focus measure.

Nuclear snRNA and nuclear function (discovery of 5' cap structures in RNA).

In view of the fact that eukaryotic gene expression starts in the nucleus, it is important to have a thorough understanding of nuclear macromolecular structure and function. Newly discovered snRNAs are eukaryotic cell specific and have unique subnuclear compartmental localizations. There are over 200 nucleolar-specific RNAs that include some abundant U3, U8, and U13 RNAs. Extranucleolar-nuclear-specific RNAs (snRNA) are 4.5S RNA I, II, III, 5S RNA III, U1, U2, U4, U5, and U6, in addition to over 500 different RNA species reported up to now. In particular, some snoRNAs and snRNAs have trimethylguanosine cap structures that are not present in bacteria. They have crucial roles in gene expression, such as transcription (U3 snoRNA), processing (U3, U8, U13, U14, U22, and 7-2/MRP), methylation (U14-16, U18, U20-21, and U24-63), pseudouridylation (E2, E3, U19, U23, and U64-72), and hnRNA splicing (U1, U2, U4, U5, and U6 snRNA).

A novel human ERK phosphatase regulates H-ras and v-raf signal transduction.

A cDNA encoding a novel human extracellularly-regulated kinase (ERK) phosphatase, designated B59, was isolated from a B5/589 human mammary epithelial cell cDNA library. The 1104 nucleotide open reading frame encodes 368 amino acids including the highly conserved catalytic site sequence of protein phosphotyrosine phosphatases (PTPs), VXVHCXXGXXR, at amino acid position 276-287. The predicted 70 amino acid stretch surrounding the HC motif shares significant sequence identity with other human dual specificity PTPs (dsPTPs), including the known ERK PTPs CL100, PAC1, B23, as well as the dsPTPs VH-1 and VHR. B59 protein synthesized in vitro in a rabbit reticulocyte lysate dephosphorylated rat ERK1 and ERK2 proteins whose phosphorylation had been stimulated by v-mos kinase added to the lysate. Ectopic expression of B59 in NIH3T3 fibroblasts inhibited the induction of an oncogene-responsive promoter by the dominant-activating raf mutant, raf-BXB. Moreover, cotransfection of NIH3T3 cells with B59 inhibited morphological transformation by H-ras and v-raf oncogenes. These results suggest that B59 suppresses the transforming activity of H-ras or v-raf oncogenes through ERK dephosphorylation and inactivation.

Effect of naftifine on neutrophil adhesion.

Effective methods of fungal treatment involve reduction in fungal infections and host inflammatory responses. Naftifine (NF), a topical antifungal agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. Additionally NF has been shown to inhibit polymorphonuclear leukocyte (PMN) chemotaxis and respiratory burst activity in an irreversible dose-dependent and time-dependent manner. Since leukocyte adherence to endothelia is believed to be one of the initial crucial events in the recruitment of circulating leukocytes to the site of inflammation, we have investigated the in vitro effect of NF on PMN adherence to nylon fiber, BSA-coated glass chamber or polystyrene, and endothelial monolayers via three adherence assays. All three assays demonstrated a statistically significant reduction (p < 0.01-0.001) in PMN adherence to the respective media. In particular, NF (at 30-60 micrograms/ml) significantly inhibited PMN adherence to endothelial monolayers (p < 0.01) as measured spectrophotometrically by the uptake of rose bengal stain. Therefore, NF inhibits PMN adherence to endothelia in our in vitro model system. This inhibition may constitute part of the anti-inflammatory effect of NF.

Beneficial effect of serum on the fertilizability of mouse oocytes matured in vitro.

Mouse oocytes matured in vitro in chemically defined medium were not penetrated by spermatozoa. The time required for dissolution of the zona pellucida of such oocytes by alpha-chymotrypsin was much longer than that for ovulated oocytes. Addition of fetal calf serum to the medium for maturation of oocytes improved the incidence of sperm penetration and shortened the time of enzymic dissolution of the zona pellucida. These results suggest that the low rate of fertilization of oocytes matured in vitro is mainly due to qualitative changes of the zona pellucida, which could be overcome by a factor or factors in fetal calf serum.

Postprandial glucose and insulin responses to glucose polymers by premature infants.

Previous studies have questioned whether neonatal infants can digest and absorb glucose polymers (GP). Thirteen infants of 33-42 weeks of corrected gestational age were fed two glucose polymers with different dextrose equivalents (DE) and glucose. Postprandial glucose and insulin responses were measured consecutively after each feeding. At 60 min, glucose, glucose polymer DE 15 and glucose polymer DE 24 produced serum glucose responses of 138.1, 111.6 and 120 mg/100 ml, respectively. Differences in mean serum glucose and insulin levels were found when glucose or glucose polymers were used as the test carbohydrate. Glucose polymer DE 24 produced a hormonal response closer to that of glucose. This suggests that glucose polymers were hydrolyzed and absorbed and evoked a sufficient glucose and insulin response. Therefore, these glucose polymers would seem to be suitable for use in feeding neonatal infants.

Natural history of parainfluenza virus infection in childhood.

In order to determine the natural history of parainfluenza virus infection in early life, we followed prospectively 130 infants and children from birth or a few months of age for evidence of infection with PV. Using rapid diagnostic techniques, standard tissue culture infectivity, and serologic techniques we were able to document primary PV infection in 92% of these infants, and repeated infection with heterotypic or homotypic PV strains in 49% by 30 months of age. Increasing patient age had no significant effect in reducing the incidence of lower respiratory tract illness as a result of PV infection. Infection with one PV serotype provided no protection against LRTI at the time of subsequent infection with a heterotypic PV strain. In contrast, primary PV infection provided a brief period of immunity to LRTI upon homotypic reinfection. Secretory IgA responses to PV were determined by immunofluorescent techniques. Antibody response to PV strains causing primary infection and heterotypic repeated infection were transient and of low magnitude. Homotypic reinfection resulted in significantly enhanced production of secretory antibody to PV. At least in early life, repeated exposures to PV appear to be essential for maintaining immunity to severe forms of illness caused by PV infection.

The development of pancreatic function in premature infants after milk-based and soy-based formulas.

Thirty-one premature infants who required nasojejunal feeding were evaluated for pancreatic exocrine function before and after feeding of milk-based or soy-based formulas for 30 days. The two groups were well matched for age and birth weight (about 1.5 kg). At birth, all infants had high basal secretion of trypsin and chymotrypsin, but low lipase and no amylase activity. Additionally, there was no response to pancreozymin (CCK). After 30 days of feeding with either soy or milk-based formulas, both groups showed a similar increase in body weight (to 1.8 kg) and basal secretion of trypsin, chymotrypsin, and lipase and failure to secrete amylase. The group that was fed milk-based formula failed to respond to CCK and secretin administration. Thus, soy- and milk-based formulas result in similar weight gain and similar basal pancreatic enzyme secretion while feeding with soy-based formula selectively increases the trypsin and lipase response to CCK.

The fibrinolysin system and its relationship to disease in the newborn.

The fibrinolysin system is incomplete in newborn infants. Lack of serum plasminogen in premature newborn has an important role in the pathophysiology of the respiratory distress syndrome since alveolar fibrin deposits cannot be eliminated. Urokinase activated human plasmin has increased the survival rate of infants with respiratory distress syndrome. Plasminogen given I.V. at birth has reduced the incidence and the severity of respiratory distress syndrome, in a randomized double-blind study of 500 premature infants. Death in the plasminogen recipient group occurred only among infants born to mothers with bleeding complications of pregnancy. Plasmin inhibitors measured with a functional assay were the highest in this group of infants, serum plasminogen was the lowest; when activator and purified human plasminogen were added to the serum, fibrinolytic activity was elicited in excess of the plasminogen added. It is suggested that plasminogen and/or plasmin inhibitors may be abnormal fetal variants in infants born to mothers with bleeding complications.

Prevention of hyaline membrane disease with plasminogen. A cooperative study.

In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.

Prevention of hyaline membrane disease with plasminogen. Preliminary report of a cooperative study.

Five hundred premature infants were treated in a double blind, randomized study with intravenous plasminogen or placebo within 60 minutes of birth. There was a significant decrease in severe clinical respiratory distress, death due to hyaline membrane disease and total mortality in the plasminogen treated infants as compared to the controls.

Effects of alpha-amanitin, cycloheximide, and thioacetamide on low molecular weight nuclear RNA.

Studies were made on the effects of alpha-amanitin, cycloheximide, and thioacetamide on synthesis and content of low molecular weight nuclear RNA. Cycloheximide, an inhibitor of protein synthesis and the synthesis of 45S pre-rRNA and 5S RNA, also inhibited synthesis of nuclear U1 and U3 RNAs. alpha-Amanitin, an inhibited the synthesis of U1 and U2 low molecular weight nuclear RNA. Thioacetamide, which induces nucleolar hypertrophy and increased nucleolar RNA polymerase activity, markedly increased synthesis of 5.8S RNA and U3 RNA. These results show that syntheses of individual low molecular weight nuclear (LMWN) RNAs are controlled by different regulatory mechanisms. In particular, there appears to be a specific relationship between U3 RNA and functional states of the nucleolus.

Nuclear ribonucleoprotein complexes containing U1 and U2 RNA.

Nuclear ribonucleoprotein (RNP) complexes that contain the U1 and U2 RNA of chromatin of Novikoff hepatoma cells were extracted with 0.01 M Tris-HCl (pH 8.0) after the nuclei were initially washed with 0.075 M NaCl and 0.025 M EDTA (pH 8.0). These RNP complexes were purified by chromatography on Sepharose 6B columns and centrifugation on sucrose density gradients. The identity of the U1 and U2 RNA in these particles was established by their electrophoretic mobility in polyacrylamide gels and their T1 RNase fingerprints which were identical with those of authentic U1 and U2 RNA (R. Reddy et al. (1974), J. Biol. Chem.249, 6486-6494; H. Shibata et al. (1974), Mol. Cell. Biochem. 4, 3-19). The nuclear riboncleoproteins had a buoyant density of 1.47 g/ml in CsCl gradients. Two-dimensional polyacrylamide gel electrophoresis of their proteins showed these RNP complexes contain 10 polypeptide spots, of which two are phosphorylated in vivo.