Large radiolucent lesion of the maxilla

In this cross-sectional study we investigated the effect of compressive and tensile forces applied on the proximal femur during weight-bearing activities. Ninety-seven men (29.9 +/- 1.7 years) were divided into two groups: 69 exercisers who had practiced regular high-impact weight-bearing activities for at least 5 years and 28 controls who had been sedentary for at least 5 years. The maximum isometric hip abduction strength was measured. The bone mineral density (BMD) of the femoral neck and the greater trochanter was assessed using dual-energy X-ray absorptiometry (DXA). Controls were considered as the reference population to calculate the Z score. Mean BMD values of the femoral neck were 0.97 g/cm2 on both sides in the exercisers and 0.83 g/cm2 on the right side and 0.84 g/cm2 on the left side in the controls. Mean BMD values of the greater trochanter were 0.86 g/cm2 on the right side and 0.87 g/cm2 on the left side in the exercisers, 0.73 g/cm2 on the right side and 0.72 g/cm2 on the left side in the controls. The BMD was significantly higher in exercisers at both trochanteric and cervical sites (P = 0. 0001). Both left and right hip abduction strength was significantly greater in the exercisers than in the controls (P < 0.05) and was positively correlated to cervical and trochanteric BMD (P < 0.01). In the exerciser group, the trochanteric Z score was higher than the cervical Z score at both right (P = 0.06) and left (P = 0.002) sides. Therefore, the proximal femoral BMD was significantly greater in exercised subjects as compared with sedentary controls. The difference was observed at the level of both the femoral neck (where it is known anatomically that only compressive gravitational forces are exerted) and the greater trochanter (where it is known that tensile forces are exerted). This result suggests the participation of both compressive and tensile forces in the mechanisms by which exercise influences bone trophicity.     

Determinants of plasma levels of plasminogen activator inhibitor-1 : A study of normotensive twins

We investigated whether plasma levels of the plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) are genetically determined in monozygotic (MZ) and dizygotic (DZ) twins. Twenty-five pairs of healthy twins underwent measurements of PAI-1:Ag and other variables, including body mass index, mean blood pressure, plasma renin activity, insulin, and glucose. To ascertain the zygosity of twins, highly discriminating micro- and minisatellite systems with variable numbers of tandem repeats were analyzed by PCR amplification followed by polyacrylamide gel electrophoresis. Subjects were also genotyped for the 4G/5G polymorphism by PCR. Estimates of genetic variance and heritability were obtained for PAI-1:Ag, and for body mass index, mean blood pressure, plasma renin activity, glucose, and insulin by jointly examining data in a path analysis with TWINAN90. Results showed that 12 pairs of twins were MZ and 13 were DZ. All tests of genetic variance [within pair (WP): F=6.24, P=0.002; among component (AC): F=2.62, P=0.04; average absolute difference t test=3. 00, P=0.004] showed significant genetic variance of PAI-1:Ag, but not of the other variables. Three tests of heritability (WP=0.837, P=0.002; AC=1.791, P<0.05; intraclass correlation: 1.180, P=0.001) consistently showed significant PAI-1:Ag heritability. Additive genetic influences (A), dominance genetic effect (D), and random environmental influences (E) accounted for 0.714, 0.154, and 0.132 of PAI-1:Ag variance, respectively. No effect of different 4G/5G genotypes was found. Thus, these results show significant genetic variance and heritability of PAI-1:Ag and suggest that A is more important than both D and E in determining PAI-1:Ag variance.     

An outcrossed canine pedigree for linkage analysis of hip dysplasia

Twenty-four hip replacements were performed with use of a medial protrusio technique to stabilize the fit of a hemispherical metal shell in the acetabulum in nineteen patients who had dysplasia of the hip. All of the hips were followed for a minimum of five years (average, seven years; range, five to thirteen years). Six of the hips were type I, seven were type II, eight were type III, and three were type IV according to the criteria of Crowe et al. The acetabular cup was implanted with the medial aspect of its dome beyond the Kohler line (drawn from the ischium along the ilioischial line) in all hips. An autogenous graft sculpted from the femoral head was used to cover 15 to 30 percent of the superolateral portion of the cup in one type-I hip, four type-III hips, and one type-IV hip. The need for these six bone grafts could have been avoided by reaming two to three millimeters more medially or by allowing 20 percent of the superolateral portion of the cup to be uncovered. Sixty to 84 percent of each bone graft was resorbed, effectively leaving the superolateral portion of the cup uncovered. The amount of the surface of the cup that was beyond the Kohler line averaged 41 percent for the six type-I hips, 43 percent for the seven type-II hips, 41 percent for six of the type-III hips, and 44 percent for one of the type-IV hips. Crossing of the ilioischial and iliopubic lines was noted on the radiographs of two type-III and two type-IV hips. Radiographs of two type-I hips and one type-II hip showed 7 to 17 percent of the surface of the dome of the cup through the internal pelvic wall (beyond the iliopubic line). None of the twenty-four metal shells were revised. A reoperation was performed on two hips to exchange a worn polyethylene insert, and three femoral components that had been fixed without cement were revised because of mechanical loosening. Wear averaged 0.26 millimeter per year in the fourteen hips that had a titanium femoral head and 0.09 millimeter per year in the nine hips that had a cobalt-chromium femoral head. The remaining hip had a ceramic femoral head, and the wear rate was 0.09 millimeter per year. The medial protrusio technique is a predictable, reproducible method for obtaining fixation of a porous-coated, hemispherical acetabular component in a dysplastic acetabulum. The technique permits the use of a porous-coated (bone-ingrowth) component; avoids the use of support bone graft and thereby reduces the operative time; facilitates rehabilitation by permitting earlier weight-bearing of the hip; and permits the use of a modular bearing surface, which may allow future exchange of only this surface rather than revision of the entire acetabular component because of excessive wear.     

Favorable effects of flecainide in transvenous internal cardioversion of atrial fibrillation

OBJECTIVES: The aim of the study was to evaluate the effects of intravenous (IV) flecainide on defibrillation energy requirements in patients treated with low-energy internal atrial cardioversion. BACKGROUND: Internal cardioversion of atrial fibrillation is becoming a more widely accepted therapy for acute episode termination and for implantable atrial defibrillators. METHODS: Twenty-four patients with atrial fibrillation (19 persistent, 5 paroxysmal) underwent elective transvenous cardioversion according to a step-up protocol. After successful conversion in a drug-free state, atrial fibrillation was induced by atrial pacing; IV flecainide (2 mg/kg) was administered and a second threshold was determined. In patients in whom cardioversion in a drug-free state failed notwithstanding a 400- to 550-V shock, a threshold determination was attempted after flecainide. RESULTS: Chronic persistent atrial fibrillation was converted in 13/19 (68%) patients at baseline and in 16/19 (84%) patients after flecainide. Paroxysmal atrial fibrillation was successfully cardioverted in all the patients. A favorable effect of flecainide was observed either in chronic persistent atrial fibrillation (13 patients) or in paroxysmal atrial fibrillation (5 patients) with significant reductions in energy requirements for effective defibrillation (persistent atrial fibrillation: 4.42+/-1.37 to 3.50+/-1.51 J, p < 0.005; paroxysmal atrial fibrillation: 1.68+/-0.29 to 0.84+/-0.26 J, p < 0.01). In 14 patients not requiring sedation, the favorable effects of flecainide on defibrillation threshold resulted in a significant reduction in the scores of shock-induced discomfort (3.71+/-0.83 vs. 4.29+/-0.61, p < 0.005). No ventricular proarrhythmia was observed for any shock. CONCLUSIONS: Intravenous flecainide reduces atrial defibrillation threshold in patients treated with low-energy internal atrial cardioversion. This reduction in threshold results in lower shock-induced discomfort. Additionally, flecainide may increase the procedure success rate in patients with chronic persistent atrial fibrillation.     

Enhanced interaction of HLA-DM with HLA-DR in enlarged vacuoles of hereditary and infectious lysosomal diseases

Following biosynthesis, class II MHC molecules are transported through a lysosome-like compartment, where they acquire antigenic peptides for presentation to T cells at the cell surface. This compartment is characterized by the presence of HLA-DM, which catalyzes the peptide loading process. Here we report that the morphology and function of the class II loading compartment is affected in diseases with a phenotypic change in lysosome morphology. Swollen lysosomes are observed in cells from patients with the hereditary immunodeficiency Chediak-Higashi syndrome and in cells infected with Coxiella burnetii, the rickettsial organism that causes Q fever. In both disease states, we observed that HLA-DR and HLA-DM accumulate in enlarged intracellular compartments, which label with the lysosomal marker LAMP-1. The distribution of class I MHC molecules was not affected, localizing disease effects to the endocytic pathway. Thus, cellular mechanisms controlling lysosome biogenesis also affect formation of the class II loading compartment. Analysis of cell surface class II molecules revealed that their steady-state levels were not reduced on diseased cells. However, in both disease states, enhanced interaction between HLA-DR and HLA-DM was detected. In the Chediak-Higashi syndrome cells, this correlated with more efficient removal of the CLIP peptide. These findings suggest a mechanism for perturbation of Ag presentation by class II molecules and consequent immune deficiencies in both diseases.     

Studies on the Origin of Amylose and Amylopectin in Starch Granules. I. The Use of Polytoma uvella as a Source of NDPG-Glucosyltransferases and some Properties of the Enzymes

The alga Polytoma uvella was found to be a good source of both soluble and starch-bound NDPG-glucosyltransferase. The properties of the enzymes were similar to those of transferases from other plant sources, but differed in some respects. ADPG and UDPG acted as glucose donors, while maltose was inactive as glucose acceptor. Acetone preparations of the soluble enzyme were stable, but β-amylase could not be completely removed without inactivating the transferase. They also contained oligosaccharides of the maltose series.     

Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are the leading causes of maternal and fetal morbidity/mortality. The central deficit in both conditions is impaired placentation due to poor trophoblast invasion, resulting in a hypoxic milieu in which oxidative stress contributes to the pathology. We examine the factors driving the hypoxic response in severely preterm PE (n = 19) and IUGR (n = 16) placentae compared to the spontaneous preterm (SPT) controls (n = 13) using immunoblotting, RT-PCR, immunohistochemistry, proximity ligation assays, and Co-IP. Both hypoxia-inducible factor (HIF)-1α and HIF-2α are increased at the protein level and functional in pathological placentae, as target genes prolyl hydroxylase domain (PHD)2, PHD3, and soluble fms-like tyrosine kinase-1 (sFlt-1) are increased. Accumulation of HIF-α-subunits occurs in the presence of accessory molecules required for their degradation (PHD1, PHD2, and PHD3 and the E3 ligase von Hippel–Lindau (VHL)), which were equally expressed or elevated in the placental lysates of PE and IUGR. However, complex formation between VHL and HIF-α-subunits is defective. This is associated with enhanced VHL/DJ1 complex formation in both PE and IUGR. In conclusion, we establish a significant mechanism driving the maladaptive responses to hypoxia in the placentae from severe PE and IUGR, which is central to the pathogenesis of both diseases.     

Influence of neonatal idiopathic respiratory distress syndrome on serum enzyme activities in premature healthy and asphyxiated newborns

Elevated serum aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), and hydroxybutyrate dehydrogenase (HBDH) activities are highly predictive for the development of hypoxia-related neurologic disorders in asphyxiated newborns. Little is known about the influence of the idiopathic respiratory distress syndrome (IRDS) on the serum profile of these enzymes. In a prospective study we measured ASAT, LDH, and HBDH activities in asphyxiated newborns with (n = 12) and without (n = 12) IRDS as well as non-asphyxiated newborns with IRDS (n = 16). Blood samples were taken serially at five fixed times: 0 (cord), 12, 24, 72, and 144 hours postpartum. Whereas both study groups of asphyxiated newborns showed significantly elevated enzyme activities as compared with the non-asphyxiated controls, the fundamental influence of perinatal hypoxic-ischemic events on neonatal serum enzyme profiles and activities of all three enzymes was not significantly altered by the development of IRDS. Therefore, the predictive value of these enzymes for the development of neurologic disorders in asphyxiated newborns is not adversely affected by the development of an immediately and effectively treated IRDS. It is concluded that elevated ASAT, LDH, and HBDH activities can be used as predictors for neurologic disorders in asphyxiated newborns even in the presence of IRDS.     

The small heat shock protein HSP27 is not an independent prognostic marker in axillary lymph node-negative breast cancer patients

Heat shock protein 27 (hsp27) belongs to the family of heat shock proteins and is thought to be involved in thermotolerance, cell proliferation, drug resistance, and chaperone processes. The aim of this study was to investigate whether hsp27 levels are correlated with clinical outcome in axillary lymph node-negative breast cancer patients. We describe a Western blot study measuring hsp27 levels in 425 patients and an immunohistochemistry (IHC) study analyzing 788 patients. Results obtained by both methods were concordant. Univariate survival analysis was performed considering hsp27 either as an optimally dichotomized variable or as a continuous variable. Additional data include age at biopsy, tumor size, estrogen receptor (ER) and progesterone receptor status, tumor ploidy and percentage of cells in S phase, and adjuvant therapy. hsp27 levels correlated positively with ER status (P = 0.0001 in Western blot and IHC study), progesterone receptor status (P = 0.0001 in Western blot and IHC study), and aneuploidy (Western blot study, P = 0.0012; IHC study, P = 0.0004) but not with tumor size (Western blot study, P = 0.69; IHC, P = 0.53) or S phase (Western blot study, P = 0.19; IHC study, P = 0.38). Overall, there was no relationship between hsp27 expression and disease-free survival (Western blot study, P = 0.70/0.54; IHC, P = 0.47/0.30) or overall survival (Western blot study, P = 0.16/0.15; IHC, P = 0.46/0.78). Exploratory subset analyses defined by ER status and use of adjuvant treatment indicated that in ER+/untreated patients, high hsp27 levels correlated modestly with shorter disease-free survival (Western blot, P = 0.04/0.04; IHC, P = 0.11/0. 03). hsp27 is not a useful prognostic marker for the clinic in axillary lymph node-negative patients. However, the finding of modest prognostic value of hsp27 in the subgroup of ER+/untreated patients raises new questions about the biological function of hsp27 in breast cancer.