Sisters, brothers, and delinquency: evaluating social influence during early and middle adolescence.

Although a number of studies have shown that brothers are highly correlated for delinquent behavior, much less research has been conducted on sisters. We propose that sisters, like brothers, show notable similarity for delinquent behavior, and also promote each other's delinquency through direct interaction. We examined these issues in 164 brother and sister pairs studied over a 4-year period (from early to middle adolescence) in a study of intact families in the rural Midwest. Sibling similarity for self-reports of delinquent behavior were highly correlated for both brothers and sisters. Conditional effects of high levels of hostile-coercive sibling relationships and older sibling delinquency predicted younger sibling delinquency in both brother and sister pairs. For brothers, conditional effects were also detected for high levels of warmth-support, in contrast to sisters. The conditional effects of older sibling delinquency and relationship quality were shown to predict change in younger sibling delinquency through adolescence. The results add to a growing literature on sibling effects as well as theoretical models that emphasize the role of social interaction between siblings as a risk factor for the development of delinquent activity in adolescence.

Pathways of economic influence on adolescent adjustment.

An important part of a science aimed at the prevention of human dysfunction involves the development of empirically based models that identify processes of risk for or protection from emotional distress or behavioral problems over time. The present study developed and evaluated such a model that proposed two pathways through which family economic pressure was expected to influence change in adolescent internalizing symptoms (depression and anxiety) during the period from the eighth to the tenth grades. A total of 377 rural families in a midwestern state provided data for the analyses. The results were generally consistent with the conceptual model in that family economic pressure increased adolescent perceptions of family economic hardship, which, in turn, reduced the adolescent's sense of control or mastery over time. Lowered mastery was associated with increases in emotional distress. Also consistent with the model, prior levels of mastery appeared to reduce the magnitude of economic stress experienced by the adolescent, whereas prior emotional distress intensified the economic stress process. Although gender differences were found in these processes, the overall pattern of results suggests that girls and boys are both at risk for internalizing problems when families experience economic pressure. Implications of the findings for the development of effective preventive interventions with financially stressed families in rural areas are discussed.

Human papillomavirus DNA replication. Interactions between the viral E1 protein and two subunits of human dna polymerase alpha/primase.

Papovaviruses are valuable models for the study of DNA replication in higher eukaryotic organisms, as they depend on host factors for replication of their DNA. In this study we investigate the interactions between the human papillomavirus type 11 (HPV-11) origin recognition and initiator protein E1 and human polymerase alpha/primase (pol alpha/primase) subunits. By using a variety of physical assays, we show that both 180- (p180) and 70-kDa (p70) subunits of pol alpha/primase interact with HPV-11 E1. The interactions of E1 with p180 and p70 are functionally different in cell-free replication of an HPV-11 origin-containing plasmid. Exogenously added p180 inhibits both E2-dependent and E2-independent cell-free replication of HPV-11, whereas p70 inhibits E2-dependent but stimulates E2-independent replication. Our experiments indicate that p70 does not physically interact with E2 and suggest that it may compete with E2 for binding to E1. A model of how E2 and p70 sequentially interact with E1 during initiation of viral DNA replication is proposed.

Concomitant EEG, lactate, and phosphorus changes by 1H and 31P NMR spectroscopy during repeated brief cerebral ischemia.

Pilots of high-performance aircraft are subject to transient loss of consciousness due to cerebral ischemia resulting from sudden high gravitational stress. To assess the effects of gravitational stress-induced blackout on cerebral metabolism and electrical function, we developed an animal model in which global cerebral ischemia is produced repeatedly at short intervals. Rats were prepared by ligation of subclavian and external carotid arteries and the right carotid artery was cannulated bidirectionally to measure circle of Willis and systemic pressures. Ischemia was induced by inflation of an occluder about the left carotid artery. Interleaved 31P and 1H NMR spectra were acquired on a 4.7-T Biospec system simultaneously with EEG recordings. We report results from 20 experiments of 30-min duration in which rats were subject to 30 1-min ischemia:reflow cycles of 10I:50R, 20I:40R, 30I:30R, and 40I:20R [numbers are seconds of ischemia (I) and reflow (R) during each 1-min cycle]. During ischemia the graded delivery of the ischemic insult permitted direct correlations between 2- to 5- and 7- to 20-Hz EEG activity and progressive changes in pH, lactate, ATP, phosphocreatine (PCr) and Pi. The best correlations were found between EEG activity and pH and PCr; correlation coefficients ranged from 0.93 to 0.95. A loss of EEG activity was observed without significant sustained energy loss in all but the most severe cycle.

Evaluation of lactate production and clearance kinetics by 1H NMR in a model of brief repetitive cerebral ischemia.

Pilots of high-performance aircraft are subject to repeated transient cerebral ischemia during high-gravitational stress maneuvers. Previously we have demonstrated that repeated episodes of transient cerebral ischemia and reflow are cumulative and lactate accumulations appear to be exponential. To evaluate the metabolic events determining the kinetics of lactate accumulation, and therefore the rates of substrate utilization, we have used in vivo 1H nuclear magnetic resonance with a 5-s time resolution to measure lactate production and clearance. The individual rates for each animal were then used to predict the accumulation of lactate in the same animal during 30 episodes of ischemia and reflow. Lactate accumulation was modeled as the balance between a zero-order production process during the ischemic period and a first-order clearance process. The predicted lactate accumulation showed excellent agreement with the observed time course, validating the predictive power of the simple model used. The highly reproducible nature of this model and its accuracy in predicting lactate accumulation should enable more accurate studies of the deleterious effects of lactate accumulation in cerebral ischemia by providing a highly reproducible means for generating a specific level of lactate accumulation.

ATP and pH predictors of histologic damage following global cerebral ischemia in the rat.

In vivo changes of high energy phosphates and pH were determined with 31P NMR spectroscopy in rats subjected to symmetric or asymmetric partial global ischemia with reperfusion. Tissue damage was assessed by histology. ATP depletion, following PCr depletion, developed shortly after the onset of ischemia. In prolonged ischemia reperfusion was not followed with full recovery. APT depletion of more than 20% during reperfusion was associated with histologic damage; marked necrosis was associated with 50% reduction. Although during ischemia, severe persisting intracellular acidosis developed sometimes, and it was also associated with tissue damage, it did not appear to elicit tissue damage independently of the ATP depletion. Splitting of the Pi peak was useful in predicting heterogeneous distribution of the necrosis, thus it can reflect a heterogeneous distribution of the intracellular pH.

A mathematical model of the intracerebral steal phenomenon in regional and focal ischaemia.

The objective of the present work was to mathematically estimate the extent and dynamics of intracerebral steal which may occur in response to cerebral vasodilation in regional and focal cerebral ischaemia. To this end, a spatially distributed mathematical model of regional cerebral blood flow (rCBF) was developed. The model contained a parallel system of intracerebral vascular resistances which were connected in series to a lumped extracerebral artery resistance and, for the focal ischaemia model, also a lumped pial collateral resistance. The rCBF was measured at 30 min of ischaemia in the following models: (1) bilateral carotid occlusion in spontaneously hypertensive rats (SHR), and (2) occlusion of the middle cerebral artery (MCA) in normotensive rats. The measured 3-dimensional rCBF data were used to set up the initial values of intracerebral resistance components. Cerebral vasodilation induced by inhalation of CO2 was simulated in the model by decreasing the values of both intracerebral and collateral resistance. Vascular responsiveness was specified to decrease with the ischaemic rCBF. In addition, a long term change in rCBF and resistance distribution was introduced to account for: (1) gradual rise in intracerebral resistance due to ischaemic oedema, and (2) adaptive decrease in collateral resistance. The following were predicted by the mathematical model. (1) At 60% maximum intracerebral dilatation a small intracerebral steal (5-10%) occurs at flow levels below 30-50 ml/100 g/min in both ischaemic models. (2) In focal ischaemia, the steal can be compensated by the 5% to 20% decrease in the collateral vascular resistance. (3) The rate of collateral adaptation overcomes the rate of intracerebral resistance rise and, therefore, eliminates the intracerebral steal after an adequately long period of time (on the order of a few hours). (4) An inverse steal effect can be demonstrated at the end of vasodilatation, provided that the time constant of collateral adaptation selected is longer (about 5:1) than the time constant of the intracerebral resistance rise. We conclude that the prediction of rCBF response to vasodilatation in cerebral ischaemia requires a knowledge of resting rCBF and of the response characteristics of both intracerebral and pial arterial segments.

A family process model of economic hardship and adjustment of early adolescent boys.

We propose a family process model that links economic stress in family life to prosocial and problematic adolescent adjustment. Employing a sample of 205 seventh-grade boys aged 12 to 14 years (M = 12.7) and living in intact families in the rural Midwest, the theoretical constructs in the model were measured using both trained observer and family member reports. In general, results were consistent with the proposed model. Objective economic conditions such as per capita income and unstable work were related to parents' emotional status and behaviors through their perceptions of increased economic pressures such as the inability to pay monthly bills. These pressures were associated with depression and demoralization for both parents, which was related to marital conflict and disruptions in skillful parenting. Disrupted parenting mediated the relations between the earlier steps in the stress process and adolescent adjustment. The emotions and behaviors of both mothers and fathers were almost equally affected by financial difficulties, and disruptions in each parent's child-rearing behaviors had adverse consequences for adolescent development.

The contribution of reoxygenation to ischemic brain damage.

This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue PO2% was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum electrodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the PO2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 microns of each of 19 electrode sites among seven rats was evaluated histologically. There was a positive correlation between reoxygenation level and severity of neuronal damage. Perineuronal lucent halo formation, probably representing astrocyte foot process swelling, was negatively correlated with reoxygenation level. This study demonstrates that ischemic neuronal damage was aggravated by increased reoxygenation but that perineuronal swelling, as evidenced by halo formation, was somewhat ameliorated.

Parenting factors, social skills, and value commitments as precursors to school failure, involvement with deviant peers, and delinquent behavior.

Elements of social control theory were combined with social learning theory to construct a model of delinquency which specifies the manner in which parenting factors, social skills, value commitments, and problems in school contribute to association with deviant peers and involvement in delinquent behavior. The model was tested using a sample of 61 families, each of which included a seventh grader. Questionnaire responses and coded videotaped family interaction were employed as measures of study constructs. The results largely supported the proposed model.

Histologic assessment of neurons in rat models of cerebral ischemia.

We describe a method for typing neurons into four progressive stages of ischemic deterioration based on visual characterization of the nucleus in terms of its optical contrast, delineation along the nuclear-cytoplasmic interface, and its shape. Difficulty in assessing nuclear shape required the introduction of an angularity comparator chart to improve the investigator's accuracy. Three investigators typed neurons obtained from normal, ischemic, and ischemic-reperfused rat brains. Accuracy and reproducibility of the investigators' typing decisions with and without the angularity comparator charts were evaluated. The accuracy of subjective shape assessment was compared with objective digitizer measurements of the same. The angularity comparator charts reduced subjective shape classification error by two thirds, and group error (overall performance expressed by the coefficient of variance) decreased from 15.9% to 4.7% for Type I (normal cells), from 33.9% to 17.3% for Type II (cells with angular nuclei), from 15.5% to 14.1% for Type III (cells with smeared nuclei), and from 3.2% to 5.5% for Type IV (dead cells). Thus, Type I and IV neurons can be assessed at a higher reproducibility than the intermediate Types II and III. Our typing method can also be used to evaluate the effect of treatment regimes on ischemic neuronal damage.

Classifying cells from light microscopic bit features by binary logic. Application to grade neuronal injury in cerebral ischemia.

Degradative cellular processes within neurons were analyzed and graded by a conceptually new approach that decoupled the process of subcellular feature analysis and grading, the latter being based on the severity of observed deterioration in subcellular features. Rather than evaluate the cell's histologic image in a panoramic manner, investigators were required to give simple yes-no decisions about the presence or absence of a specific pathologic feature (bit feature as opposed to panoramic analysis). Multiple elementary decisions create a binary representation of the cell image that can be easily handled and analyzed using computer techniques to generate all possible unique phenotypes of the scanned neuronal population. In the first application of this method, however, the number of possible phenotypes were reduced by imposed a priori logic on the separation scheme focusing on a single cellular structure (the nucleus) that was followed through the stages of structural decay. We experimentally validated four neuronal types of five theoretical possibilities when three nuclear bit features were used in typing. Grading of neuronal injury for groups of normal, ischemic, and ischemic and reperfused rats into two, three, and four categories are reported. The consistency at which the method can be implemented was assessed by calculating the mean and standard deviation of the reconciled typing decisions given by the four investigators. The group of the four investigators showed less than 2, 3, and 5% error when grading cells from control, ischemic, and ischemic-reperfused animals, respectively.

Patterns of EEG frequency content during experimental transient ischaemia in subhuman primates.

EEGs were recorded with depth electrodes in 8 monkeys undergoing transient middle cerebral artery ligation. Electrodes measured EEG, cerebral blood flow (CBF), and tissue oxygen simultaneously during and after occlusion. An EEG frequency analysis was performed. Electrode sites were examined microscopically, and infarction size, tissue vacuolization index, and neuronal morphology were described quantitatively. Serial neurological examinations were performed. Two patterns of EEG frequency change were delineated, dependent upon degree of ischaemia. Mild ischaemia, as indicated by less severe clinical deficits, higher CBF during occlusion, and minor pathological changes was associated with large increases in slow EEG activity and decreases in fast EEG activity during occlusion, with recovery of slow activities to baseline, but continued suppression of fast activities 24 h later. Severe ischaemia was associated with suppression of both fast and slow frequencies during occlusion, with slow activities returning to baseline and fast activities remaining suppressed 24 h later. The best quantitative EEG indicator of severity of ischaemia was suppression of slow wave activity during occlusion. The best EEG indicator that an ischaemic event had occurred 24 h previously was continued suppression of fast EEG activities. These data may be helpful in the design of EEG frequency analysis studies for monitoring the time course of human cerebral ischaemia and for retrospective diagnosis of transient ischaemic attacks (TIAs).

The role of tissue acidosis in ischaemic tissue injury: the concept of the pH integral.

Cerebral cortical tissue pH was monitored with an extracellular glass electrode in 32 rats subjected to total global cerebral ischaemia produced by ligation of the basilar and carotid arteries with systemic hypotension for periods of 8 to 60 min. The totality of the ischaemia, and its duration were confirmed by monitoring with a brain tissue O2 electrode. Reperfusion was induced by hypertension and maintained thereafter to exclude delayed ischaemia during 3 h survival after which the rats were sacrificed by perfusion fixation. The severity of tissue pH change was varied by inducing hyperglycaemia in some of the rats. Quantitative counts were made of neurons demonstrating changes reflecting severe ischaemic injury within 500 microns of the electrode tip. For the criterion of an ischaemically injured neuron count greater than 20%, there appeared to be a threshold at about 30 min, and more than 0.8 units change in pH. For quantitative assessment of the ischaemic insult a more satisfactory index was found by combining both time and acidosis as the integral of the pH change during the period of ischaemia. This was found to have a strong correlation with the histologic changes. There was a less strong correlation between the acidosis during reperfusion and the histologic change. Comparing these results with those for 3 rats subjected to 215 min of ischaemia without reperfusion, it appears that most of the effect of acidosis in aggravating ischaemic injury takes place during the first hour of ischaemia with little further aggravation for longer periods.

Computer-regulated constant pressure ischemia in the rat: the animal model.

A system permitting computer control of partial ischemia in the normotensive rat brain was developed. Right carotid cannulation and bilateral subclavian artery occlusion made the input of blood to the brain dependent solely on left carotid artery flow. Perfusion pressure was controlled by partial compression of this artery with a balloon. The system can produce a range of partial ischemic states maintaining perfusion pressures from 4 to 20 mm Hg. The adequacy of the servo-control system was evaluated in greater detail at requested perfusion pressures of 7 and 12 mm Hg in 14 male Sprague-Dawley rats (300-450 g). Experimentally obtained cerebral perfusion pressures of 6.84 (SD = 0.25, n = 7) and 11.72 (SD = 0.89, n = 7) mm Hg, respectively, demonstrate the efficacy of the system. CBFs were concurrently measured at four separate bilaterally symmetric anatomic sites (cortex, hippocampus, thalamus, and substantia nigra). Significant intra- and interhemispheric differences were found to exist, with regional flows monitored ipsilaterally to the carotid balloon exceeding those of the opposite hemisphere. In summary, this acute model of cerebral ischemia permits control of perfusion pressure over the entire critical partial ischemic range.

Mathematical analysis of network topology in the cerebrocortical microvasculature.

The three-dimensional branching pattern of deep cerebrocortical capillary networks was reconstructed from histological sections. The distribution of blood flow in a mathematical model of the reconstructed network was calculated. The transit of red blood cells through the network was simulated by computer, and the total path length traveled by the cells was estimated. The results support both anatomical and hemodynamic heterogeneity of the cerebrocortical microvascular system.

Pressure distribution in the pial arterial system of rats based on morphometric data and mathematical models.

The objective of the present work was a theoretical evaluation of pial arterial pressures in normotensive rats and spontaneously hypertensive rats based on the geometry and topography of the pial arterial system as well as on various topological models of the vascular trees. Pial branches of the middle cerebral artery in the diameter range of 30-320 microns were selectively visualized by corrosion compound, and the diameter and length of vascular segments were measured. The vessels were classified into branching orders by the methods of Horsfield and Strahler. The steady-state pressure distribution in the pial arterial system was calculated assuming that the flow at the bifurcations was partitioned in proportion to a given power of the diameters of the daughter branches (diameter exponent). The maximum number of vascular segments along the longest branch varied between 16 and 33. The mean branching ratio was 4.14 +/- 0.23 (SD). The mean diameter of vessels classified into Strahler orders 1-5 were: 50 +/- 12, 71 +/- 19, 106 +/- 22, 168 +/- 22, and 191 +/- 7 microns, respectively. The calculated pressure drop in the pial trees of normotensive rats was approximately twice as large in proximal orders 3 and 4 than in distal orders 1 and 2. The mean pressure in arteries of order 1 ranged from 54.4 to 58.4 mm Hg in the normotensive rat (input pressure: 83 mm Hg), and from 77.2 to 89.0 mm Hg in the spontaneously hypertensive rat (input pressure: 110 mm Hg). The coefficient of variation of terminal pressures in vessels of order 1 increased linearly with the mean pressure drop in the system. The coefficient of variation in terminal pressure had a minimum as a function of the diameter exponent in case of each pial tree. At its minimum, it was higher in all spontaneously hypertensive rats (10.1-22.9%) than in any normotensive rats (6.0-8.5%). The corresponding diameter exponents were in most cases lower in the spontaneously hypertensive rat (1.3-2.5) than in the normotensive rat (2.5-3.0). Topologically consistent models of the pial arterial network predicted significantly less variation in intravascular pressures than was obtained by direct calculations. More idealized models suggested the dependence of coefficient of variation in terminal pressure on the total number of vascular segments contained by the tree. All models predicted the existence of the minimum of coefficient of variation in terminal pressure in function of the diameter exponent.(ABSTRACT TRUNCATED AT 400 WORDS)

Kaposi sarcoma limited to glans penis.

Two cases of Kaposi sarcoma are presented. In each case the lesion had a bluish discoloration and was painless. Excision of lesions with wider margins was adequate therapy.