Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma

Members of the platelet-derived growth factor (PDGF) ligand family are known to play important roles in wound healing and fibrotic disease. We show that both transient and stable expression of PDGF-C results in the development of liver fibrosis consisting of the deposition of collagen in a pericellular and perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver disease. Fibrosis in PDGF-C transgenic mice, as demonstrated by staining and hydroxyproline content, is preceded by activation and proliferation of hepatic stellate cells, as shown by collagen, alpha-smooth muscle actin and glial fibrillary acidic protein staining and between 8 and 12 months of age is followed by the development of liver adenomas and hepatocellular carcinomas. The hepatic expression of a number of known profibrotic genes, including type beta1 TGF, PDGF receptors alpha and beta, and tissue inhibitors of matrix metalloproteinases-1 and -2, increased by 4 weeks of age. Increased PDGF receptor alpha and beta protein levels were associated with activation of extracellular regulated kinase-1 and -2 and protein kinase B. At 9 months of age, PDGF-C transgenic mice had enlarged livers associated with increased fibrosis, steatosis, cell dysplasia, and hepatocellular carcinomas. These studies indicate that hepatic expression of PDGF-C induces a number of profibrotic pathways, suggesting that this growth factor may act as an initiator of fibrosis. Moreover, PDGF-C transgenic mice represent a unique model for the study of hepatic fibrosis progressing to tumorigenesis.     

Cluster of deaths from group A streptococcus in a long-term care facility--Georgia, 2001

BACKGROUND: Invasive group A streptococcus (GAS) affects approximately 10,500 persons annually; 1 in 5 patients >/=65 years die. In August 2001, CDC investigated a cluster of GAS deaths in a Georgia long-term care facility (LTCF). METHODS: We screened LTCF residents and staff for GAS carriage and conducted a retrospective cohort study among residents. We defined a case as GAS isolation associated with clinical infection. RESULTS: Eight cases were identified (median age: 79 years); 6 (75%) patients died. Carriage was similar in residents (10%) and staff (9%). All isolates among residents and 63% among staff were type emm 77. Risk factors for GAS disease or carriage among residents were receiving skin treatment (relative risk [RR] = 4.0, 95% confidence interval [CI] = 1.9-11.0) and having an infected or colonized roommate (RR = 2.0, 95% CI = 1.10-5.0). No wound care nurse carried GAS. Interventions included education about standardized infection control guidelines and appropriate hand hygiene; carriers were treated with antibiotics. No subsequent GAS cases were identified in the following year. CONCLUSIONS: Transmission of GAS in this outbreak likely occurred during wound care and ended with improved hand hygiene. This investigation highlights additional research and policy needs for control of severe GAS infections among the high-risk LTCF population.     

The hypnotic dreams of healthy children and children with cancer: A quantitative and qualitative analysis

In this study, the Stanford Hypnotic Clinical Scale for Children was administered to 52 healthy children and 47 children and adolescents with cancer. Responses to the dream item of this scale were analyzed for the type and detail of imagery. The hypnotizability scores of both groups were similar. However, children with cancer reported more pleasant than unpleasant fantasy in their hypnotic dreams, and their dream reports tended to contain less fantasy and detail overall. Rescoring the dream item based on extent of fantasy and detail resulted in a lower pass rate for that item, especially for children with cancer. Regardless of health status, older children experienced more self-involvement in their hypnotic dreams compared to younger children.     

Effects of distraction on pain, fear, and distress during venous port access and venipuncture in children and adolescents with cancer.

This study evaluates the effect of self-selected distracters (ie, bubbles, I Spy: Super Challenger book, music table, virtual reality glasses, or handheld video games) on pain, fear, and distress in 50 children and adolescents with cancer, ages 5 to 18, with port access or venipuncture. Using an intervention-comparison group design, participants were randomized to the comparison group (n = 28) to receive standard care or intervention group (n = 22) to receive distraction plus standard care. All participants rated their pain and fear, parents rated participant fear, and the nurse rated participant fear and distress at 3 points in time: before, during, and after port access or venipuncture. Results show that self-reported pain and fear were significantly correlated (P = .01) within treatment groups but not significantly different between groups. Intervention participants demonstrated significantly less fear (P <.001) and distress (P = .03) as rated by the nurse and approached significantly less fear (P = .07) as rated by the parent. All intervention parents said the needlestick was better because of the distracter. The authors conclude that distraction has the potential to reduce fear and distress during port access and venipuncture.     

Phospholipase Cγ1 is required for pre‐TCR signal transduction and pre‐T cell development

Pre‐T cell receptor (TCR) signaling is required for pre‐T cell survival, proliferation, and differentiation from the CD4 and CD8 double negative (DN) to the double positive (DP) stage. However, the pre‐TCR signal transduction pathway is not fully understood and the signaling molecules involved have not been completely identified. Phospholipase Cγ (PLCγ) 1 is an important signaling molecule that generates two second messengers, diacylglycerol and inositol 1,4,5‐trisphosphate, that are important to mediate PKC activation and intracellular Ca²⁺ flux in many signaling pathways. Previously, we have shown that PLCγ1 is important for TCR‐mediated signaling, development and T‐cell activation, but the role of PLCγ1 in pre‐TCR signal transduction and pre‐T cell development is not known. In this study, we demonstrated that PLCγ1 expression level in pre‐T cells was comparable to that in mature T cells. Deletion of PLCγ1 prior to the pre‐TCR signaling stage partially blocked the DN3 to DN4 transition and reduced thymic cellularity. We also demonstrated that deletion of PLCγ1 impaired pre‐T cell proliferation without affecting cell survival. Further study showed that deficiency of PLCγ1 impaired pre‐TCR mediated Ca²⁺ flux and Erk activation. Thus our studies demonstrate that PLCγ1 is important for pre‐TCR mediated signal transduction and pre‐T cell development.     

Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy

Journal of Clinical Immunology - Granulocyte transfusions are sometimes used as adjunctive therapy for the treatment of infection in patients with chronic granulomatous disease (CGD). However,...     

Psychological adjustment of women with HIV/AIDS: Racial and ethnic comparisons

The relationship of race and ethnicity with standardized measures of depressive symptomatology and mental health was examined in a sample of HIV-infected African American (n = 48), Puerto Rican (n = 50), and White non-Hispanic (n = 48) women in New York City. Mean scores of women from all three racial and ethnic groups were higher than those reported for normative samples on measures of depressive symptomatology and psychological distress, and mean scores on measures of psychological well-being were lower. Puerto Rican women reported significantly higher levels of depressive symptomatology than either African American or White women. Puerto Rican women also reported significantly higher levels of psychological distress and lower levels of psychological well-being than African American women. The findings suggest that while all HIV-infected women are at risk of poor adjustment, Puerto Rican women may be especially vulnerable. They also point to the need for future research to determine what factors in these women's lives are predictive of adjustment, especially those factors amenable to intervention. © 1998 John Wiley & Sons, Inc.     

Relapsing diabetes can result from moderately activating mutations in KCNJ11

Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro.     

Repetition priming and recognition memory in younger and older persons: temporal stability and performance

The dissociation between intact priming and reduced explicit memory in aging has been called into question on the basis of limited information that suggests that priming measures are less reliable than explicit memory measures. No aging study to date, however, has offered a comprehensive examination of the reliability of these measures. Age-related performance and test-retest stability coefficients for multiple priming and explicit memory tasks were compared. Age effects were found on some tasks but not others, and stability was not related to task performance. Stability was similar for implicit versus explicit task instructions, younger versus older persons, and studied versus unstudied items. Results indicate that dissociations between priming and explicit memory performances cannot be accounted for by differential reliability of the measures.