Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells.

The extracellular matrix secreted by cultured bovine smooth muscle cells (BSMC) contains an endothelial type plasminogen activator (PA) inhibitor. When PA is incubated with the matrix, a high molecular weight complex containing a truncated PA inhibitor is released into the supernatant. The inhibitor also dissociates from the matrix by treatment with glycine, pH 2.7, in its intact, functionally active, 45-kD form, whereas treatment of the matrix with thrombin results in the release of a cleaved, inactive, 41 kD PA inhibitor. Bowes melanoma cells but not smooth muscle cells cultured on BSMC matrices decrease available matrix associated PA inhibitor. PA inhibitor incorporated into the extracellular matrix may serve an important role in the regulation of plasminogen activator mediated matrix degradation.     

Catheter-associated fungemia due to Wangiella (Exophiala) dermatitidis.

We describe a case of catheter-associated Wangiella (Exophiala) dermatitidis fungemia in a human immunodeficiency virus-infected child who was successfully treated with antifungal therapy and catheter removal. Catheter-associated W. dermatitidis fungemia appears to be distinct from previously described cases of disseminated infection with organ involvement.     

Vector-averaged gravity alters myocyte and neuron properties in cell culture.

To investigate whether changes in the gravitational field of developing neurons and myocytes affect cellular development, we rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat. Rotation in the clinostat produces, from the cells' perspective, a "vector-free" gravity environment by continuous averaging of the vector. In this way, rotation in the clinostat simulates the microgravity of space where the gravity vector is substantially reduced. At rotation rates of 1-50 rpm, cellular and nuclear areas of myocytes were significantly enlarged and the number of presumptive nucleoli increased. In neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after cessation of rotation. Since our data are generally consistent with findings from other cell types subjected to spaceflight, we suggest that the vector-free gravity environment of the clinostat appears to simulate, at least in part, the microgravity of space. Our data further show that cellular processes are sensitive to altered gravity and suggest that cell development in the microgravity of space may be significantly altered.     

Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group.

Monosomy 7 or deletions of 7q are associated with many myeloid disorders; however, the significance of such abnormalities in childhood acute lymphoblastic leukemia (ALL) is unknown. Among 1880 children with ALL, 75 (4%) had losses involving chromosome 7, 16 (21%) with monosomy 7, 41 (55%) with losses of 7p (del(7p)), 16 (21%) with losses of 7q (del(7q)), and two (3%) with losses involving both arms. Patients with losses involving chromosome 7 were more likely to be > or =10 years old, National Cancer Institute (NCI) poor risk, and hypodiploid than patients lacking this abnormality. Patients with or without these abnormalities had similar early response to induction therapy. Event-free survival (EFS) and survival for patients with monosomy 7 (P<0.0001 and P=0.0007, respectively) or del(7p) (P<0.0001 and P=0.0001, respectively), but not of patients with del(7q), were significantly worse than those of patients lacking these abnormalities. The poorer EFS was maintained after adjustment for a Philadelphia (Ph) chromosome, NCI risk status, ploidy, or an abnormal 9p. However, the impact on survival was not maintained for monosomy 7 after adjustment for a Ph. These results indicate that the critical region of loss of chromosome 7 in pediatric ALL may be on the p-arm.     

Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team

CONTEXT: Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. OBJECTIVE: To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. DESIGN: The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. SETTING: Pediatric HIV research clinics in the United States and Puerto Rico. PATIENTS: Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years. INTERVENTIONS: Children were randomized to receive zidovudine, 160 mg/m2 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m2 2 times per day (n = 100); or ritonavir, 350 mg/m2 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). MAIN OUTCOME MEASURE: Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. RESULTS: At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels (<400 copies/mL) compared with 52% and 54% of patients in the 2- and 3-drug ritonavir-containing groups, respectively (P<.001). Through study week 48, 70% of children continued receiving their ritonavir-containing regimen. At study week 48, 42% of children receiving ritonavir plus 2 nucleosides compared with 27% of those receiving ritonavir and a single nucleoside had undetectable HIV RNA levels (P = .04); however, similar proportions in each group continuing initial therapy had HIV RNA levels of less than 10000 copies/mL (58% vs 48%, respectively; P = .19). CONCLUSIONS: In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48.     

Profiles of caregiving behaviors among children and adolescents with perinatally acquired HIV

Although parenting behaviors are widely considered an important factor in the adjustment of children and adolescents with chronic physical health needs, few studies have addressed this topic as it pertains to youth with perinatally-acquired human immunodeficiency virus (PHIV). We examined profiles of child-centeredness, control through guilt, consistent discipline, and detachment, and whether these profiles differed in terms of parent- and youth-reported psychiatric disorder symptoms in a cohort of HIV infected youth (N?=?314). Latent profile analyses of caregiving behaviors were conducted separately for children (6–12 years) and adolescents (13–18 years). Two profiles were identified among children: (a) moderate caregiving (87%, n?=?130) and (b) high detachment caregiving (13%, n?=?19), and three profiles were identified among adolescents: (a) moderate caregiving (55%, n?=?88), (b) high detachment caregiving (19%, n?=?30), and (c) high control through guilt caregiving (26%, n?=?42). The high detachment and high control through guilt caregiving profiles displayed higher levels of parent-and youth-reported symptoms than the moderate caregiving profile. These findings suggest that caregiver behaviors of PHIV youth vary as a function of children’s developmental period and differ in terms of youth psychological symptoms.     

Discovery of a cholecystokinin-gastrin-like signaling system in nematodes

Members of the cholecystokinin (CCK)/gastrin family of peptides, including the arthropod sulfakinins, and their cognate receptors, play an important role in the regulation of feeding behavior and energy homeostasis. Despite many efforts after the discovery of CCK/gastrin immunoreactivity in nematodes 23 yr ago, the identity of these nematode CCK/gastrin-related peptides has remained a mystery ever since. The Caenorhabditis elegans genome contains two genes with high identity to the mammalian CCK receptors and their invertebrate counterparts, the sulfakinin receptors. By using the potential C. elegans CCK receptors as a fishing hook, we have isolated and identified two CCK-like neuropeptides encoded by neuropeptide-like protein-12 (nlp-12) as the endogenous ligands of these receptors. The neuropeptide-like protein-12 peptides have a very limited neuronal expression pattern, seem to occur in vivo in the unsulfated form, and react specifically with a human CCK-8 antibody. Both receptors and ligands share a high degree of structural similarity with their vertebrate and arthropod counterparts, and also display similar biological activities with respect to digestive enzyme secretion and fat storage. Our data indicate that the gastrin-CCK signaling system was already well established before the divergence of protostomes and deuterostomes.