Consequences of depression during adolescence: marital status and marital functioning in early adulthood

In previous studies, depression has been associated with both marital status and marital distress. Unfortunately, given the cross-sectional design of most of this research, the temporal nature of these associations is unclear. The authors examined the marital functioning of young adults as a function of whether they received psychiatric diagnoses of major depressive disorder or nonaffective psychiatric disorder during adolescence. Depression during adolescence was found to predict higher rates of marriage among younger women and subsequent marital dissatisfaction. This pattern of results appears to be specific to depression: The presence during adolescence of a nonaffective psychiatric disorder was unrelated to subsequent marital functioning. These findings highlight the potentially adverse consequences of depression in adolescence and underscore the importance of prevention and early treatment efforts.     

Effect of hydroxyethylrutosides on hypoxial-induced neutrophil adherence to umbilical vein endothelium

Thrombomodulin (TM) is a thrombin receptor on the endothelial cell surface, effective as an anticoagulant by changing procoagulant thrombin to an anticoagulant one. As rabbit TM with glycosaminoglycan (GAG) has a more potent anticoagulant activity than that without GAG, we expressed recombinant GAG-modified urinary thrombomodulin (GAG-UTM) in C-127 cells. The effect of an additional GAG chain on anticoagulant activity was investigated in comparison with unmodified recombinant UTM (r-UTM). In vitro, the activity of cleavage of fibrinogen by thrombin or prothrombinase activity was more potently depressed by GAG-UTM than by r-UTM, and the generation of activated protein C by TM-thrombin complex was accelerated by GAG modification. The acceleration of antithrombin III-dependent anticoagulant activity was shown only by GAG-UTM. Parameters like thrombin time, prothrombin time and activated partial thromboplastin time in human plasma were prolonged by GAG-UTM more than by r-UTM. In vivo, the effect of GAG-UTM and r-UTM in endotoxin-induced disseminated intravascular coagulation (DIC) rats was investigated using hematological parameters. GAG-UTM and r-UTM significantly reduced the decrease in fibrinogen and platelet number induced by endotoxin at the dosage of 0.1 and 1.0 mg/kg/h, respectively, suggesting that the antithrombotic effect of GAG-UTM in endotoxin-induced DIC rats was 10-fold as potent as that of r-UTM. GAG-UTM reduced the prolongation of the bleeding time induced by endotoxin, while r-UTM accelerated it. These results suggest that the addition of a GAG chain may increase availability as an anticoagulant.     

Hypolipidemic activity of boronated nucleosides and nucleotides in rodents

Base-boronated nucleoside and phosphate-boronated nucleotides were potent hypolipidemic agents in rodents, lowering both serum cholesterol and triglyceride levels. Rat VLDL and LDL cholesterol levels were generally reduced and HDL cholesterol levels were significantly elevated after 14 days dosing at 8 mg/kg/day. Tissue cholesterol, triglyceride and phospholipid levels were reduced by selected derivatives. Increased fecal excretion of lipids did not appear to be a mechanism by which these derivatives lowered serum lipids in rodents. Rather, the agents suppressed appetite and reduced the activities of rate-limiting enzymes for de novo lipid synthesis, specifically cytoplasmic acetyl CoA synthetase, squalene synthetase, and phosphatidylate phosphohydrolase with IC50 values of approximately 10(-5) m.     

Simplifying the molecular mechanisms of human papillomavirus

Human papillomaviruses are a common human pathogen responsible for diseases varying in severity from warts to cervical cancer. This article examines the functions of the viral gene products and how they interact with cellular factors to replicate themselves and cause disease.     

Increased mucosal B-lymphocyte apoptosis during polymicrobial sepsis is a Fas ligand but not an endotoxin-mediated process

Sepsis is reported to induce an increase in the rate of apoptosis (Ao), in immature lymphoid cells residing in hematopoietic tissues such as the thymus and bone marrow. Alternatively, secondary lymphoid tissue, such as the spleen exhibit little innate (unstimulated) Ao. However, it is unknown whether or not polymicrobial sepsis has any effects on the frequency of Ao in mucosal lymphoid tissue and what, if any, are the functional consequences of such a change. To assess this, Peyer's patch cells were harvested from C3H/HeN (endotoxin-sensitive) mice killed 12 or 24 hours after the onset of polymicrobial sepsis (cecal ligation and puncture [CLP]). The results indicate that the percentage of cells that were Ao+ as determined by flow cytometry were markedly increased at 24 hours, but not at 12 hours post-CLP. This correlates well with evidence of increased DNA fragmentation as well as histological changes observed both at a light and transmission electron microscopic level of the Peyer's patch Ao. Phenotypically, these changes were restricted to the B220+ (B-cell) population that also exhibited a marked increase of Fas/Apo-1 antigen expression. The functional consequence of this increased apoptosis appears to be associated with the endogenous stimulation (activation) of IgA production by mucosal B lymphocytes and increased nuclear c-Rel expression. Furthermore, we found that Peyer's patch lymphocytes isolated from C3H/HeJ-Faslgld (endotoxin-tolerant/Fas ligand- [FasL] deficient) as opposed to C3H/HeJ (endotoxin-tolerant) inbred mice did not exhibit increased Ao after CLP. These findings indicate that increased B-cell Ao appears to be a FasL-Fas antigen-mediated process, but is not due to endotoxin sensitivity. In conclusion, we speculate that the increased Fas-associated apoptosis detected in mucosal B cells (as opposed to splenic or bone marrow B cells) may be due to increased luminal antigens other than endotoxin, released due to gut barrier integrity breakdown during sepsis.     

Degradation of Fatigue Properties of Weld-Bonded Aluminum Exposed to Moisture and Elevated Temperature

Experiments have been completed in order to characterize the fatigue behavior of weld-bonded aluminum 5754-O/bis-phenol-A epoxy adhesive joints subjected to 100% relative humidity at 38°C. It was found that the presence of water vapor at elevated temperature decreases the fatigue strength of weld-bonded joints by as much as 33% at 5 × 10⁶ cycles. Optical microscopy, scanning electron microscopy, dynamic mechanical analysis, and tensile testing of fatigued specimens and exposed bulk adhesive revealed that fatigue strength degradation is mainly due to the plasticization and micro-cracking of adhesive by the water vapor.     

The timing of prehensile movements in subjects with cerebral palsy

Gaseous insufflation of oxygen via the venous vascular system is thought to be an useful tool for preventing anoxic tissue injury during extended time periods of ischemic preservation and for allowing for an improved recovery of organ function after transplantation. The present study aimed at the application of a noninvasive technique for monitoring effectiveness and homogeneity of gaseous areation by using an epiillumination microscopic technique for assessment of tissue nicotinamide adenine dinucleotide (NADH) fluorescence. Rat livers were flushed with and stored in University of Wisconsin solution at 4 degrees C for 48 h (n = 20). In half of the experiments (n = 10) gaseous oxygen was applied subsequent to organ harvest. Using ultraviolet-excitation high-resolution microscopy and computer-assisted image analysis liver surfaces were scanned for NADH intensity and spatial heterogeneity at 1, 24, and 48 h preservation time. Livers simply stored without aeration served as controls (n = 10). NADH intensity data were compared with corresponding data of tissue adenosine triphosphate (ATP) concentrations determined enzymatically. NADH fluorescence already differed at 1 h preservation between the two groups with significantly lower values in the aerobically stored livers. NADH fluorescence further decreased between 1 and 24 h preservation and remained low until 48 h, whereas in the anaerobically stored livers NADH fluorescence was found to be constantly high over the entire observation period. Aerobic storage resulted in rather homogeneous tissue oxygenation with an intrahepatic variation of NADH fluorescence <20%. In parallel, oxygen persufflation appropriately restored tissue ATP content within 1 to 24 h of preservation, while the simply stored livers exhibited pronounced depletion of ATP. We demonstrate for the first time that by means of retrograde gaseous oxygenation, ischemic livers can be readily and effectively oxygenated. Our study further indicates that the noninvasive microscopic analysis of tissue NADH fluorescence may be an useful tool for estimating efficiency of strategies in organ preservation.     

Pharmacokinetics of recombinant human interferon-alpha 2a combined with 5-fluorouracil in patients with advanced colorectal carcinoma

A cohort study was conducted to estimate the risk of breast cancer recurrence among women diagnosed with ductal carcinoma in situ (DCIS) and to identify tumor or patient characteristics that influence that risk. A population-based cancer registry was used to identify a cohort of 709 female residents of western Washington who were diagnosed with DCIS between January 1980 and June 1992 and were treated with breast-conserving surgery. Information about breast cancer recurrences, treatment, and several patient characteristics and exposures was obtained from postal questionnaires. Recurrences were confirmed using information from the cancer registry or hospital pathology reports. Approximately 15% of women experienced a recurrence within the first 5 years after diagnosis [95% confidence interval (CI), 12-18%]; 31% had a recurrence within 10 years (95% CI, 24-38%). There was a suggestion that risk was slightly elevated for women with larger tumors (> or =1.5 cm) and tumors of comedo subtype. Relative risks (RRs) were elevated for women who were premenopausal at diagnosis of DCIS (RR = 2.3; 95% CI, 1.1-5.0). Women in the upper decile of body mass index were at twice the risk of a recurrence as those women in the lower four deciles (RR = 2.3; 95% CI, 1.1-4.8). There was also a suggestion that women who used menopausal hormones for at least 2 years after their diagnosis of DCIS were at increased risk of recurrence compared to nonusers of menopausal hormones (RR = 1.8; 95% CI, 0.7-5.0). Our results suggest that the risk of recurrence may be related to some tumor characteristics as well as the hormonal milieu of the patient at or after her diagnosis of DCIS. However, larger studies are needed to more clearly document predictors of disease recurrence after DCIS.     

Electrophysiology of rabbit ventricular myocytes following sustained rapid ventricular pacing

The present study examined changes in electrophysiological properties of ventricular myocytes isolated from rabbit hearts after 2-3 weeks of rapid ventricular pacing. Left ventricular end-diastolic pressure at completion of the pacing period was nearly four-fold greater than in age-matched controls, although there was no significant change in heart weight/body weight ratio. Action potentials recorded in current-clamp mode at low stimulation frequencies were significantly longer in duration and phase 1 diminished in isolated myocytes from paced hearts compared with control. In voltage-clamp experiments. L-type Ca2+ current (ICa) density was not different between groups of myocytes, but the maximum current (at + 10 mV) elicited by 10 microM isoproterenol was approximately 40% less in myocytes from paced hearts. In contrast, maximum ICa elicited by 10 microM forskolin was similar in both groups. The 4-aminopyridine-sensitive transient outward current (Ito) was 65% less (at + 60 mV) in myocytes from paced hearts than from control. However, after approximately 24 h in culture, Ito density in these myocytes returned toward control values. Despite marked reduction in Ito density, the inward rectifier current (IK1) was not different between groups. These data demonstrate that Ito is significantly and reversibly decreased in myocytes from rapidly paced hearts, which may partly account for marked changes in action potential morphology. Although basal ICa was not altered in this group of myocytes compared with control, its modulation by beta-agonists was markedly blunted, probably through a decrease in receptor density or coupling to adenylyl cyclase. These changes in myocyte K+ and Ca2+ channel behavior in paced hearts may relate to impaired contractility and arrhythmogenesis that is characteristic of the intact failing heart.