Ubiquitin and apoptosis in the corpus luteum of the marmoset monkey (Callithrix jacchus)

The thiazolidinedione analogue troglitazone is an antidiabetic agent that improves insulin resistance in rodents and humans. Although coronary artery disease is common in patients with the insulin resistance syndrome, the effects of troglitazone on smooth muscle cells (SMC) have not been fully elucidated. We therefore examined the effects of troglitazone on cell growth and glucose uptake in human aortic SMC. Mitogen-activated protein (MAP) kinase activity and glucose transporter (Glut) 1 mRNA levels were also studied. In the absence of troglitazone, insulin (10(-7) M) caused a 2-fold increase of DNA synthesis in SMC and troglitazone suppressed the increase of DNA synthesis in a dose-dependent manner. This growth suppression was accompanied by inhibition of MAP kinase activity. On the other hand, troglitazone significantly increased Glut 1 mRNA and enhanced glucose uptake in SMC. These results suggest that troglitazone affects the insulin signaling pathways in SMC and suppresses growth while promoting glucose uptake. Our findings support the application of troglitazone as an inhibitor of SMC proliferation in patients with insulin resistance.     

Severe progressive deformities after limb lengthening in type-II fibular hemimelia

Until recently the accepted treatment of choice for severe type-II fibular hemimelia has been Syme's or Boyd's amputation. The alternative of distraction lengthening using the Ilizarov technique is now available. We report three patients (four limbs) with type-II fibular hemimelia who were treated by the Ilizarov technique and followed up for two to six years. Severe progressive procurvatum and valgus deformity of the tibia and valgus deformity and lateral subluxation of the ankle were found in all four limbs. Multiple additional soft-tissue and bony surgery was necessary. In view of these problems we feel that reappraisal of the indications for lengthening in type-II fibular hemimelia is necessary.     

Protective factors in adolescent health behavior

The role of psychosocial protective factors in adolescent health-enhancing behaviors--healthy diet, regular exercise, adequate sleep, good dental hygiene, and seatbelt use--was investigated among 1,493 Hispanic, White, and Black high school students in a large, urban school district. Both proximal (health-related) and distal (conventionality-related) protective factors have significant positive relations with health-enhancing behavior and with the development of health-enhancing behavior. In addition, in cross-sectional analyses, protection was shown to moderate risk. Key proximal protective factors are value on health, perceived effects of health-compromising behavior, and parents who model health behavior. Key distal protective factors are positive orientation to school, friends who model conventional behavior, involvement in prosocial activities, and church attendance. The findings suggest the importance of individual differences on a dimension of conventionality-unconventionality. Strengthening both proximal and distal protective factors may help to promote healthful behaviors in adolescence.     

Neonatal sciatic palsy: etiology and outcome of 21 cases

INTRODUCTION: Sciatic nerve paralysis is a rare entity in the newborn. Few reference in specialized tests indicate that in the majority of cases the sciatic palsy has been observed after misplaced injections into the buttocks. The prognosis is variable and appears to be better after umbilical vessel catheterization for injection of medications than after misplaced muscular injections. In case of recovery it takes place within 3 to 12 months. OBJECTIVE: The objective of the present study is to know the evolution of neonatal sciatic palsy and to determine their injury noxe in regard to perinatal factors, and their relationship with long-time outcome, and to look for prognostic clues of clinical utility. MATERIAL AND METHODS: We evaluated perinatal factors of newborn children with sciatic nerve paralysis, followed for more than 18 months of clinical evolution, in a neuropediatric centre. RESULTS: Twenty one newborn with such criteria were evaluated. Gestational age was within 32 and 42 weeks (median 38.2). The birth weight was between 2,100 and 4,100 g (median 2,973). The majority of cases obtained total recovery (16 of 21). The time of recovery was 4 to 14 months (median 8.8). Free ambulation was obtained by all cases (at 10 to 24 months). No apparent cause was observed in the majority of cases. Cesarean delivery was more frequent specially in cases with permanent consequences. CONCLUSION: Long-time prognostic of neonatal sciatic palsy is generally good. In our series all the cases with consequences were associated to cesarean delivery. The duration of cesarean intervention and the anesthesic hypotony of the newborn could be implicated in the sciatic nerve injury of poor outcome.     

Prevalence and role of anticardiolipin antibodies in Crohn disease

OBJECTIVES: Anticardiolipin antibodies belong to the group of antiphospholid antibodies, and may be seen in association with endothelial damage and recurrent vascular thrombosis. The aim of our study was to determine in patients with Crohn's disease the frequency of anticardiolipin antibodies, and to correlate their presence with clinical activity and treatment of the disease. METHODS: One hundred and thirty-eight sera from patients with Crohn's disease and 118 from age-matched controls were tested for IgG anticardiolipin antibodies. In the Crohn's disease group, we determined whether the patients had a past history of vascular thrombosis, a clinically active intestinal disease, or a current immunosuppressive therapy (steroids or azathioprine). RESULTS: Anticardiolipin antibodies were found significantly more often in patients with Crohn's disease than in controls: 11.0% versus 2.5%, P < 0.02. Three patients with Crohn's disease had a past history of vascular thrombosis, but none of them had anticardiolipin antibodies. The presence of anticardiolipin antibodies was not correlated with the fact that patients had a clinically active disease (P = 0.77), or a current immunosuppressive therapy at the time of the serological test (P = 0.95). CONCLUSIONS: There is a significantly high prevalence of patients with anticardiolipin antibodies during Crohn's disease. The positivity of the test does not seem to be correlated to the existence of a past history of vascular thrombosis, nor to the clinical activity of the disease.     

Evidence for separate effects of U73122 on phospholipase C and calcium channels in human platelets

U73122 ((1-[6-(( 17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)exyl]-1H-p yrrole-2,5-dione)) is generally used as a selective inhibitor of phospholipase C (PLC) and the related rise in cytosolic Ca2+. Recently, by using hepatocytes, it was suggested that its action sites are different for PLC activation and increase in Ca2+ concentration. To verify whether U73122 has different sites for inhibiting PLC activation and calcium responses in human platelets, aggregation, Mn2+ influx, cytosolic Ca2+ increase and PLC activation were studied in response to thrombin and the synthetic agonist of the thromboxane receptor U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2alpha). With both agonists, U73122 inhibited aggregation, Mn2+ influx and the enhancement of cytosolic calcium at concentrations of 2 microM or lower, while 10 microM was necessary to inhibit PLC activation. Our results suggested that U73122 is much more active in antagonizing Ca2+ channels, both the intracellular ones, which are activated by formation of inositol 1,4,5 P3 and those present on plasma membrane, than in reducing the activation of PLC.     

Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis

We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria. No significant differences were noted among the subtypes for ratio of males to females; age; or exposure to toxins, alcohol, or both. However, compared with the patients in the M6a group, patients in the M6b and M6c groups demonstrated a statistically significant increase in cytogenetic aberrations, proliferation markers (proliferating cell nuclear antigen and Ki67), and ringed (type III) sideroblasts. Marked survival differences were noted between the M6a (30.1 +/- 29.5 months) and M6b (3.15 +/- 4.2 months) groups, with patients in the M6c group demonstrating an intermediate prognosis (10.5 +/- 12.7 months). Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group. However, the patients in the M6c group remained in remission for a significantly shorter period of time than did patients in the M6a group. Overall, survival appeared to depend on the ratio of pronormoblasts to myeloblasts at diagnosis and demonstrated a rapid decline with increasing pronormoblast and decreasing myeloblast counts. We must, therefore, devise chemotherapeutic regimens that target both blastic components of this disease.     

Cardiac dysrrhthmia in systemic disease

This is an ECG of a 6-year-old girl. She presented to us for management of epilepsy. Magnetic resonance imaging (MRI) of the brain showed multiple lesions consistent with cortical and subcortical tubers. There were also achromic spots on her skin and echocardiography demonstrated a rhabdomyoma near the right ventricular outflow tract. A diagnosis of tuberous sclerosis, an autosomal-dominantly inherited condition, was made. What is abnormal about the ECG?     

Fast and one-step folding of closely and distantly related homologous proteins of a four-helix bundle family

Bovine acyl-coenzyme A binding protein is a four-helix bundle protein belonging to a group of homologous eukaryote proteins that binds medium and long-chain acyl-coenzyme A esters with a very high affinity. The three-dimensional structure of both the free and the ligated protein together with the folding kinetics have been described in detail for the bovine protein and with four new sequences reported here, a total of 16 closely related sequences ranging from yeasts and plants to human are known. The kinetics of folding and unfolding in different concentrations of guanidine hydrochloride together with equilibrium unfolding have been measured for bovine, rat and yeast acyl-coenzyme A binding protein. The bovine and rat sequences are closely related whereas the yeast is more distantly related to these. In addition to the three natural variants, kinetics of a bovine mutant protein, Tyr31 --> Asn, have been studied. Both the folding and unfolding rates in water of the yeast protein are 15 times faster than those of bovine. The folding rates in water of the two mammalian forms, rat and bovine, are similar, though still significantly different. A faster unfolding rate both for rat and the bovine mutant protein results from a lower stability of the native states of these. These hydrophobic regions, mini cores, have been identified in the three-dimensional structure of the bovine protein and found to be formed primarily by residues that have been conserved throughout the entire eukaryote evolution from yeasts to both plants and mammals as seen in the sample of 16 sequences. The conserved residues are found to stabilize helix-helix interactions and serve specific functional purposes for ligand binding. The fast one-step folding mechanism of ACBP has been shown to be a feature that seems to be maintained throughout evolution despite numerous differences in sequence and even dramatic differences in folding kinetics and protein stability. The protein study raises the question to what extent does the conserved hydrophobic residues provide a scaffold for an efficient one-step folding mechanism.