Reproducibility of weaning parameters. A need for standardization. Although weaning parameters can accurately predict weaning outcome, variability of the measurements of these parameters has not been closely examined. In the current study, we examined the reproducibility of these parameters using a standardized technique. Before the weaning trial, maximal inspiratory pressure (PImax), minute ventilation (VE), respiratory frequency (f), tidal volume (VT), rapid shallow breathing index (f/VT), and vital capacity (VC) were obtained on three trials over a period of 15 min. The results of these parameters over three measurements were compared. There were no statistical differences in the values of PImax, VE, f, VT, and f/VT over three trials (p = 0.45, p = 0.37, p = 0.69, p = 0.64, p = 0.1, respectively). The VC was the only parameter that showed statistical differences among three trials (p < 0.05). For the group, respiratory frequency had the lowest coefficient of variation (COV = SD/mean x 100 percent) at 6.7 percent while the VC had the highest COV at 19.6 percent. We concluded that most weaning parameters of breathing pattern can be measured reliably with bedside instruments using a standard technique.


A nurse-directed protocol using pulse oximetry to wean mechanically ventilated patients from toxic oxygen concentrations. The usual method of weaning mechanically ventilated patients from high FIO2 in our ICU, in which housestaff ordered all ventilator changes in an unstandardized manner (control group), was compared to a nurse-directed protocol that used a single arterial blood gas (ABG) analysis and multiple pulse oximetry measurements. The protocol required an ABG to be obtained upon the initiation of intubation/mechanical ventilation, followed by pulse oximetry measurements obtained in accordance with a standardized timetable. Decreases in FIO2 were guided by these results. It was concluded that a nurse-directed oxygen weaning protocol utilizing a combination of a single ABG and multiple pulse oximetry measurements was safe, reduced the need for ABGs, and decreased the duration of patient exposure to toxic oxygen concentrations.


Extracorporeal circulation as an alternative to open-chest cardiac compression for cardiac resuscitation. Open-chest direct cardiac compression represents a more potent but highly invasive option for cardiac resuscitation when conventional techniques of closed-chest cardiac resuscitation fail after prolonged cardiac arrest. We postulated that venoarterial extracorporeal circulation might be a more effective intervention with less trauma. In the setting of human cardiac resuscitation, however, controlled studies would be limited by strategic constraints. Accordingly, the effectiveness of open-chest cardiac compression was compared with that of extracorporeal circulation after a 15-min interval of untreated ventricular fibrillation in a porcine model of cardiac arrest. Sixteen domestic pigs were randomized to resuscitation by either peripheral venoarterial extracorporeal circulation or open-chest direct cardiac compression. During resuscitation, epinephrine was continuously infused into the right atrium, and defibrillation was attempted by transthoracic countershock at 2-min intervals. Systemic blood flows averaged 198 ml.kg-1.min-1 with extracorporeal circulation. This contrasted with direct cardiac compression, in which flows averaged only 40 ml.kg-1.min-1. Coronary perfusion pressure, the major determinant of resuscitability on the basis of earlier studies, was correspondingly lower (94 vs 29 mm Hg). Extracorporeal circulation, in conjunction with transthoracic DC countershock and epinephrine, successfully reestablished spontaneous circulation in each of eight animals after 15 min of untreated ventricular fibrillation. This contrasted with the outcome after open-chest cardiac compression, in which spontaneous circulation was reestablished in only four of eight animals (p = .038). We conclude that extracorporeal circulation is a more effective alternative to direct cardiac compression for cardiac resuscitation after protracted cardiac arrest.


Lung sequestration. Diagnosis with ultrasound and triplex Doppler technique in an adult. The application of chest US with triplex Doppler technique to detect the systemic feeding artery of lung sequestration in an adult patient is described. To our best knowledge, this is the first description of the use of this technique to diagnose pulmonary sequestration in adult patients. This 35-year-old man had necrotizing pneumonia with abscess formation at the left lower lobe. Chest US demonstrated a large tortuous vessel in the central part of the lesion. Spectral wave Doppler analysis showed that this vessel was a systemic feeding artery and had pulsatile arterial wave-form. The color Doppler mapping delineated the blood flow originating from the descending aorta and toward the lesion, thus confirming the diagnosis of pulmonary sequestration. We conclude that chest US with triplex Doppler technique is a valuable method in evaluating a patient with a pulmonary lesion who was thought to have lung sequestration before performing invasive aortography.


Evolving aortic mass in a patient with sepsis and systemic embolization. Detection by transesophageal echocardiography. An elderly patient with sepsis and systemic embolization is described. An intraluminal aortic mass was discovered by transesophageal echocardiography that appeared to be the source of infection in this patient. Transesophageal echocardiography can be a useful diagnostic test in patients with sepsis and systemic embolization of unknown etiology.


Inflammatory pseudotumor of the heart with vasculitis and venous thrombosis. Inflammatory pseudotumor (IPT) is a tumor-like reactive lesion of unknown etiology. An unusual case of intracardiac IPT with multisystemic involvement, including leukocytoclastic vasculitis, polyarthritis, and inferior vena cava thrombosis in a 17-year-old boy is reported. This unique combination may suggest that immune/autoimmune factors are important in the pathogenesis of IPT.


Utility of transesophageal echocardiography in the conservative management of prosthetic valve endocarditis. Prosthetic valve endocarditis is a formidable complication following cardiac valve replacement. Surgical intervention has resulted in a significant reduction in mortality when certain complications prevail. We report two such cases of prosthetic valve endocarditis in which the use of transesophageal echocardiography permitted close surveillance during medical therapy and thus avoided the need for surgical intervention. Therefore, with the improved ability to monitor disease progression with transesophageal echocardiography, nonsurgical management of prosthetic valve endocarditis remains an option.


Tension pneumopericardium in an infant.

Tension pneumopericardium in an infant. Pneumopericardium in newborns is most often a complication of mechanical ventilation and frequently results in fatal cardiac tamponade. We report the case of a mechanically ventilated 33-day-old full-term gestation infant with interstitial pneumonitis who developed tension pneumopericardium. Treatment includes lowering peak inspiratory pressure and decompressing the pericardial space with tube drainage following pericardiocentesis.


Intravenous pentamidine-induced bronchospasm. A 41-year-old man with AIDS developed a recurrence of Pneumocystis carinii pneumonia and was treated with intravenous pentamidine. This was associated with a significant bronchospastic reaction requiring treatment with an antihistamine and an aerosolized beta-agonist therapy. To our knowledge, this is the first report of bronchospasm induced by intravenous pentamidine.


Paradoxical bradycardia during exercise and hypoxic exposure. The possible direct effect of hypoxia on sinoatrial node activity in humans. We describe a patient with pulmonary emphysema who developed paradoxical cardiodeceleration not only during incremental exercise associated with hypoxemia but also during progressive hypoxic challenge. Since coronary angiogram revealed no abnormality, this unique phenomenon seemed to be due to the direct effect of hypoxia on the sinus node activity.


Malignant lymphoma in a patient with relapsing bronchiolitis obliterans organizing pneumonia. A case of relapsing bronchiolitis obliterans organizing pneumonia complicated by malignant lymphoma (four years after the diagnosis) is reported in a 58-year-old woman. To our knowledge, such an association has not been described previously in detail in the literature.


Reversible left ventricular dysfunction induced by recurrent ventricular tachycardia. Two cases of transient LV dysfunction associated with VT are described. Both patients had a history of palpitations of several years' duration without symptoms of congestive heart failure. The reason for presentation was an increase in frequency and duration of palpitation. Decreased LV wall motion, observed by 2DE, normalized shortly after treatment of the VT. Diffusely decreased LV wall motion is associated with frequent episodes of VT and may mimic DCM except that signs and symptoms of heart failure are absent.


Coexistent sarcoidosis and HIV infection. A comparison of bronchoalveolar and peripheral blood lymphocytes. A case of pulmonary sarcoidosis diagnosed in an human immunodeficiency virus (HIV)-infected man is reported. The transbronchial lung biopsy specimen revealed noncaseating granuloma. A comparison of the lymphocyte subsets in both peripheral blood and bronchoalveolar lavage fluid revealed a pattern more typical of HIV infection than of classic sarcoidosis. A course of prednisone led to improvement in symptoms, roentgenographic findings, lung volumes, and diffusion capacity.


Mediastinal bronchogenic cyst. A cause of upper airway obstruction. Although bronchogenic cysts may involve the mediastinum, they have rarely been responsible for significant upper airway obstruction. We describe a young man who had a rapidly expanding cervical mass due to the migration of a mediastinal bronchogenic cyst. Flow-volume loops confirmed the presence of a variable intrathoracic obstruction. The patient rapidly developed respiratory failure requiring urgent intubation and surgical resection.


Thoracoscopic Nd:YAG laser resection of a solitary pulmonary nodule. Advances in endoscopic surgical techniques and laser technology have expanded the role of thoracoscopy. We report a thoracoscopic resection of a benign pulmonary lesion. A 44-year-old man underwent a successful Nd:YAG laser-assisted thoracoscopic resection of a peripheral lung hamartoma. The patient's postoperative course was uncomplicated. Thoracotomy with its attendant morbidity was avoided. Continued success with thoracoscopic resection will have a significant impact on the management of select patients with peripheral, solitary pulmonary nodules.


Hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis induced by penicillin. A 54-year-old Japanese man demonstrated a sultamicillin-induced hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis. A positive lymphocyte stimulation test for sultamicillin and a decreased CD4/CD8 ratio of lymphocytes in BAL fluid suggested that an alteration in cell-mediated mechanisms was responsible for the patient's symptoms.


Giant thoracoabdominal lymphangioma with features of lymphangiomyoma. A 15-year-old girl who presented with cough and dyspnea was found to have a mediastinal tumor that clinically resembled a lymphangioma. The tumor was unusual for its large size and its histologic features, which showed smooth muscle proliferation, generally considered a feature of lymphangiomyoma.


Sterile mediastinal gas mimicking abscess in aortic aneurysm repair. Six weeks after aortic aneurysm repair, computed tomography (CT) showed mediastinal gas where absorbable gelatin sponge (Gelfoam) was used. A leukocyte scan labeled with indium 111, however, was normal and surgical exploration showed no infection. Sterile gas collections may be seen following absorbable gelatin sponge use many weeks after surgery and 111In-labeled leukocyte scanning may be a useful differential test.


Pulmonary Hodgkin's disease in HIV-infected patient. Diagnosis by bronchoalveolar lavage. We report herein the pulmonary recurrence of Hodgkin's disease coincidental with a marked decrease in the peripheral blood CD4 lymphocyte count in an HIV-seropositive patient with alveolar consolidation on chest roentgenogram. The diagnosis of lung parenchyma involvement was made by bronchoalveolar lavage cell analysis and illustrates the reliability of Reed-Sternberg cell identification in bronchoalveolar lavage for the diagnosis of pulmonary localization of Hodgkin's disease.


Children of lesbian and gay parents.

Children of lesbian and gay parents. This paper reviews research evidence regarding the personal and social development of children with gay and lesbian parents. Beginning with estimates of the numbers of such children, sociocultural, theoretical, and legal reasons for attention to their development are then outlined. In this context, research studies on sexual identity, personal development, and social relationships among these children are then reviewed. These studies include assessment of possible differences between children with gay or lesbian versus heterosexual parents as well as research on sources of diversity among children of gay and lesbian parents. Research on these topics is relatively new, and many important questions have yet to be addressed. To date, however, there is no evidence that the development of children with lesbian or gay parents is compromised in any significant respect relative to that among children of heterosexual parents in otherwise comparable circumstances. Having begun to respond to heterosexist and homophobic questions posed by psychological theory, judicial opinion, and popular prejudice, child development researchers are now in a position also to explore a broader range of issues raised by the emergence of different kinds of gay and lesbian families.


Multiple influences on the acquisition and socialization of children's health attitudes and behavior: an integrative review. An overview and synthesis of the literature documenting various influences on the socialization and acquisition of children's health attitudes and behavior is the focus of this review. Cognitive-developmental approaches to understanding children's health attitudes are presented, followed by an exploration of an individual differences perspective on children's acquisition of health attitudes and behavior. The influence of various socialization agents, including families, peers, schools, and the media, on children's acquisition of health attitudes and behavior is considered. Implications of these findings for social policy, future research, and modeling of child health attitudes and behavior are examined.


The development of category-based induction. In a category-based induction, knowing that a property is true of some category members leads one to conclude that the property is true of other category members. An example is: Cardinals have ulnar arteries. Therefore hawks have ulnar arteries. Recently, Osherson et al. (1990) demonstrated a number of phenomena involving category-based inductions, and proposed that these phenomena can be explained by variations in 2 processes: (a) the similarity between the premise category (cardinals in the above example) and the conclusion category (hawks in the above example), and (b) the degree to which the premise category "covers" (roughly, is similar to) instances of the lowest-level category that includes both the premise and conclusion categories (birds in the above example). The present paper traces the developmental course of the relevant phenomena and of the similarity and coverage processes that presumably underlie them. Studies 1 and 2 demonstrated that the inductions made by kindergartners are sensitive only to the similarity between the premise and conclusion categories. Studies 3 and 4 showed that second graders' inductions are sensitive to both premise-conclusion similarity and coverage, as long as there is no need actually to use a generated category that includes both the premise and conclusion categories. These developmental findings reveal an orderly process in the growth of category-based inductions, and also decompose the Osherson et al. model into 3 basic components that have not previously been explicitly distinguished.


Infant information processing in relation to six-year cognitive outcomes. As part of a longitudinal follow-up of full-terms and preterms, infant measures of information processing obtained at 7 months and 1 year were related to various 6-year outcomes: general intelligence, language proficiency, early reading and quantitative skills, and several facets of perceptual organization (N = 91). 7-month Visual recognition memory (VRM) was associated with 6-year performance in all domains, and 3 1-year measures--VRM, cross-modal transfer (CMT), and object permanence--were related to IQ and/or one or more specific outcomes (r's = .20 to .47). Many of the infant-childhood relations remain significant even with IQ partialed. Additionally, 7-month VRM and 1-year CMT scores were lower for infants who, at 6 years, were considered at risk for learning disabilities. Overall, measures from the first year of life predicted both specific cognitive abilities and IQ at 6 years; to some extent, the specific abilities were predicted independently of IQ.


The relations between frontal brain electrical activity and cognitive development during infancy. The relations between changes in the scalp-recorded electroencephalogram (EEG) and the development of the ability to perform successfully 2 cognitive tasks attributed to frontal lobe functioning were examined in 13 infants from 7 to 12 months of age. Infants successful in performing the A-not-B task with increasingly longer delays across the second half of the first year of life showed changes in power in scalp-recorded brain electrical activity in the frontal region and an increase in anterior/posterior EEG coherence. Infants with rapid mastery of object retrieval did not differ in frontal EEG development from infants who exhibited the normal developmental progression in object retrieval performance. In a task examining inhibition of reaching to a novel toy, there were no differences in frontal EEG as a function of performance. Results from a cross-sectional sample revealed similar findings. These data confirm work with nonhuman primates on the importance of maturation of frontal cortex in the successful performance on certain tasks (A-not-B), but do not confirm nonhuman primate data on the importance of frontal cortex for other tasks (object retrieval). The data also suggest that the electroencephalogram may be useful as a noninvasive measure of central nervous system development during the first year of life.


Integration of sequential information for shape perception by infants: a developmental study. Perception of form by spatiotemporal integration was investigated in 3 experiments. In the first, infants aged 8, 10, and 12 months were tested using a novelty-preference procedure to determine the earliest age at which recognition of rectilinear and curvilinear form occurred. Infants were shown a light-point tracing of the outline of a figure, followed by simultaneous presentation of 2 test objects, one of the same shape as the tracing and one of a different shape. The tracing was double the size of the test objects. Only infants in the oldest group responded selectively by looking longer at the object of different shape. In the second experiment with 12-month-old infants only, it was shown that recognition of rectilinear, but not curvilinear, form occurred despite a difference in the orientation and size of tracing and object. Computer-generated tracings were used in the final experiment to compare form recognition for 2D and 3D stimuli. Selective responding occurred only for the latter. These findings show that by 12 months infants perceive the correspondence between the figural properties of a tracing and its extended form, but that this perception is dependent on the provision of depth cues.


Early ontogeny of vocal behavior of Japanese infants in response to maternal speech. Discriminant analysis was used to distinguish statistically between the comfort-state vocalizations uttered by Japanese infants following 5 different types of pitch contours of maternal speech. Ontogenetic changes of their vocal behaviors were investigated during the first 5 months of life. Structural variability in infant vocalizations across variants of maternal speech was found to be characterized by a set of quantifiable physical parameters. However, infant's age when a vocalization was recorded was not an important contributor. Successful attempts at cross-validation, in which the discriminant profiles derived from one sample of vocalizations were used to classify a second set of vocalizations, indicated that the result obtained was not an artifact of using the same data set to derive the profiles to test reclassification accuracy. Proportion of cross-validated vocalizations that were misclassified decreased as age increased. The results of the present study demonstrate that a statistically significant relation exists between acoustic features of maternal speech and those of following infant vocalizations, and that such a relation strengthens over age.


Intentional behavior and intentional communication in young free-ranging orangutans. The goal of this study was to describe the ontogeny of the manipulation of an animate object (i.e., the mother) by young free-ranging orangutans within the context of food sharing. The food-sharing context is an important one in the development of object manipulation skills and social communication. 5 orangutans, ranging in age from 1 month to 5 years, were videotaped with their biological mothers for 18 hours over the course of 9 months. Systematic coding of the videotapes revealed that even young orangutans, 1-6 months old, used intentional (i.e., goal-directed) behaviors. When young orangutans directed behavior toward the mother in addition to the goal object then maternal responses were positive, resulting in the infant obtaining the food. Intentional communication, evident in gestures and consisting of an abbreviated action directed toward the mother, was found in the 3 oldest orangutans (2 1/2, 3 1/2, and 5 years of age). Cognitive competence and behavioral performance are considered from the developmental perspectives of Piaget and prelinguistic communication. The ability to use a communicative gesture as an intermediate means in the coordination of actions on a social agent with actions on an object is evident in young orangutans.


Preterm children at early adolescence and continuity and discontinuity in maternal responsiveness from infancy. Patterns in mother-child interaction from infancy to age 12 were investigated in a prospective, longitudinal study of 44 English-speaking mothers and their preterm children. Maternal responsiveness was assessed by home observations during infancy and the Family Interaction Q-Sort at age 12, derived from 2 structured laboratory situations requiring cooperation of mother and child. A cluster of maternal behaviors of critical control toward the toddler was assessed at age 2 years. Children of mothers who were consistently more responsive during both infancy and early adolescence, as well as children whose mothers became more responsive by age 12, achieved higher IQ and arithmetic scores, had more positive self-esteem, and their teachers reported fewer behavioral and emotional problems than children of mothers who were consistently less responsive both during infancy and at age 12. Continuity in parenting behaviors was related to control and criticism beginning in the toddler period and not to degree of responsiveness to the infant.


The contribution of mother-child and father-child relationships to the quality of sibling interaction: a longitudinal study. Although several studies have now examined the relations between mother-child and sibling interaction, the role of fathers in the development of sibling relationships is noticeably absent. The present study included assessments of both mother-child and father-child interaction in order to examine the correlates of sibling conflict and cooperation. Home observations of parent-child and sibling interaction and reports of differential parental treatment were obtained for 30 families with 2 preschool children when the firstborns were approximately 6 years old. Earlier assessments of infant-mother and infant-father attachments when firstborns were 12 and 13 months old, respectively, were also available, as were prior laboratory assessments of mothering and fathering when the oldest child was 3 years of age. Results suggested that sibling conflict and aggression were related to high levels of conflict between the mother and the 2 children at 6 years, intrusive and overcontrolling mothering at 3 years, and an insecure infant-mother attachment. Facilitative and affectionate fathering, on the other hand, was associated with prosocial sibling interaction. Early relationship experiences between parents and their firstborn children had an enduring effect on the quality of sibling relationships and interacted with differential parental treatment in predicting sibling relationship outcomes.


Self-regulatory mechanisms governing gender development. This study tested predictions about development of gender-related thought and action from social cognitive theory. Children at 4 levels of gender constancy were assessed for their gender knowledge, personal gender standards, and gender-linked behavior under different situational conditions. Irrespective of gender constancy level, all children engaged in more same-sex than cross-sex typed behavior. Younger children reacted in a gender stereotypic manner to peers' gender-linked behavior but did not regulate their own behavior on the basis of personal gender standards. Older children exhibited substantial self-regulatory guidance based on personal standards. They expressed anticipatory self-approval for same-sex typed behavior and self-criticism for cross-sex typed behavior. Their anticipatory self-sanctions, in turn, predicted their actual gender-linked behavior. Neither gender knowledge nor gender constancy predicted gender-linked behavior. These results lend support to social cognitive theory that evaluation and regulation of gender-linked conduct shifts developmentally from anticipatory social sanctions to anticipatory self-sanctions rooted in personal standards.


Impact of parenting practices on adolescent achievement: authoritative parenting, school involvement, and encouragement to succeed. This article examines the impact of authoritative parenting, parental involvement in schooling, and parental encouragement to succeed on adolescent school achievement in an ethnically and socio-economically heterogeneous sample of approximately 6,400 American 14-18-year-olds. Adolescents reported in 1987 on their parents' general child-rearing practices and on their parents' achievement-specific socialization behaviors. In 1987, and again in 1988, data were collected on several aspects of the adolescents' school performance and school engagement. Authoritative parenting (high acceptance, supervision, and psychological autonomy granting) leads to better adolescent school performance and stronger school engagement. The positive impact of authoritative parenting on adolescent achievement, however, is mediated by the positive effect of authoritativeness on parental involvement in schooling. In addition, nonauthoritativeness attenuates the beneficial impact of parental involvement in schooling on adolescents achievement. Parental involvement is much more likely to promote adolescent school success when it occurs in the context of an authoritative home environment.


Support from spouse as mediator and moderator of the disruptive influence of economic strain on parenting. A model is presented regarding associations between economic strain, support from spouse, and quality of parenting. The model was tested using a sample of 451 2-parent families, each of which included a seventh grader (age 12-13). Parent and adolescent reports, as well as observational ratings, were used as indicators of constructs. Analysis using structural equation modeling procedures indicated that level of spouse support was positively related to supportive parenting, whereas economic strain operated to undermine parental involvement. As posited, economic strain produced its effect through a direct relation with parenting and indirectly through its association with spouse support. These findings held for mothers and fathers, regardless of the gender of the child. Spouse support moderated the impact of economic strain on supportive parenting for mothers but not fathers. Possible explanations for this gender difference are presented.


Social information processing in aggressive and depressed children. Social information processing patterns of children who were identified as being aggressive or depressed, both, or neither were compared in order to address the issue of specificity and to explore whether children who are comorbid show a unique processing style. Subjects were 220 children in the third through sixth grade. Peer nomination and teacher ratings were used to assess level of aggression, and the Children's Depression Inventory was used to measure level of depression. Aggressive children showed a hostile attributional bias, were more likely to report that they would engage in aggressive behavior, and indicated that aggression would be easy for them. Depressed children similarly showed a hostile attributional bias, although they were more likely to attribute negative situations to internal, stable, and global causes. Depressed children also reported that they would be less likely to use assertive responses and that they expected that assertive behavior would lead to more negative and fewer positive outcomes. Children who were comorbid generally showed patterns similar to both aggressive and depressed children.


Some consequences of early harsh discipline: child aggression and a maladaptive social information processing style. Although a number of studies have reported a relation between abusive parental behavior and later aggressive behavior in the victim, many of these investigations have had methodological limitations that make precise interpretation of their results problematic. In the present study, we attempted to determine whether harsh parental discipline occurring early in life was associated with later aggression and internalizing behavior in children, using a prospective design with randomly selected samples to avoid some of these methodological difficulties. Structural equation modeling indicated a consistent relation between harsh discipline and aggression in 2 separate cohorts of children. This relation did not appear to be due to possible confounding factors such as child temperament, SES, and marital violence, although there was some indication in our data that the latter variables were related to child aggression. In addition, our analyses suggested that the effect of harsh discipline on child aggression may be mediated at least in part by maladaptive social information processing patterns that develop in response to the harsh discipline.


Cognitive mechanisms in children's gender stereotyping: theoretical and educational implications of a cognitive-based intervention. The study was designed to test the hypothesis derived from cognitive-developmental theory that multiple classification skill plays an important role in children's gender stereotyping and in their processing of counterstereotypic gender information. Children (N = 75; 5-10 years) were matched on pretest measures of gender stereotyping and multiple classification skill and then assigned to: (1) multiple classification training using nonsocial stimuli, (2) multiple classification training using social stimuli, (3) a rule training intervention, or (4) a control intervention. Children who had acquired multiple classification skill via training with social stimuli and those children trained on rules for occupational sorting showed significantly more egalitarian responding on a subsequent measure of gender stereotyping and superior memory for counterstereotypic information embedded in stories. Additionally, children who had acquired multiple classification skill via training with nonsocial stimuli showed superior memory for counterstereotypic information, despite demonstrating no greater flexibility on the gender stereotyping measure. Both theoretical and educational implications of results are discussed.


Beyond beliefs: parent and child behaviors and children's perceived academic competence. Examined the relations of parent and child behaviors with children's perceptions of their academic competence. 74 high-achieving third-grade children, with varying levels of perceived academic competence, were observed working with mothers and fathers both on solvable tasks (Period 1) and during a period that included some unsolvable tasks (Period 2). Results indicated that children's perceived academic competence was positively related to father warmth, both at Period 1 and at Period 2. Children's perceived academic competence was also positively related to their own behavior when working with fathers at Period 2. Specifically, children with higher perceived academic competence showed more emotional restraint and were more self-reliant when working on tasks at Period 2 than were children with lower perceived academic competence. The results indicate that there are systematic, observable correlates of children's self-reports of their perceived academic competence.


The cross-ethnic equivalence of parenting and family interaction measures among Hispanic and Anglo-American families. Recently there has been concern over the need for developmental research within ethnic minority populations and interest in family processes within, and variability across, ethnic groups. Unfortunately, most of the research using standard scales of family processes has sampled middle-class Anglo-Americans, and the potential absence of cross-ethnic measurement equivalence threatens the validity of the research using these scales with ethnic minority populations. This study reports confirmatory factor analyses and construct validity coefficients for several parenting and family interaction scales among Anglo-American and Hispanic 8-14-year-old children and mothers. The findings indicate that the Children's Report of Parental Behavior Inventory (except the hostile control subscale), the Parent-Adolescent Communication Scale (open communication subscale only), and the Family Adaptability and Cohesion Evaluation Scales II appear to have sufficient cross-ethnic equivalence for English-speaking Hispanic samples. Further, the Family Routines Inventory and the problem communication subscale could benefit from additional scale development.


Children's relationships with maternal grandparents: a longitudinal study of family structure and pubertal status effects. This longitudinal study assessed the effects of parents' marital transitions and pubertal development on grandparent-grandchild relationships. 9- to 13-year-old children, their mothers, and maternal grandparents from 186 Caucasian, middle-class families including 73 intact families, 64 mother-custody, single-parent families and 49 stepfamilies completed questionnaires focusing on the degree of children's "relationship involvement" (perceived closeness and frequency of contact) with maternal grandparents at 2 time periods 13 months apart. Children also completed questionnaires 9 months later during a third interview. Grandparents, and especially grandfathers, were more involved with grandchildren from single-parent families (supporting the "latent function" hypothesis). The pubertal status results supported the "emotional distancing" hypothesis for grandfather-granddaughter relationships (higher pubertal status, less involvement) and the "stress buffer" hypothesis for grandsons' relationships with both grandparents (greater change in physical development, more involvement and greater perceived closeness).


Young children and television: the retention of emotional reactions. In 6 experiments, we examined preschoolers' ability to interpret or remember the affective reactions of television characters. In 2 studies, children viewed a "Sesame Street" or "Cosby Show" segment, and then retold the story. In both, mention of the protagonists' affective states was low, with less than 1% of the reactions recalled. In 3 experiments (using muppet, cartoon, or human portrayals), we examined whether this low retention was due to an inability to interpret reactions, identify their emotional labels, or remember them across a short period. For muppet and cartoon shows, children accurately recognized labels for reactions immediately after portrayal, but showed significant reductions in recognition memory by the end of the show. For human portrayals, subjects showed accurate recognition immediately after presentation, as well as after the show. In a final experiment, free descriptions of the reactions were assessed. Correct description was significantly higher for basic emotions than complex emotions.


Temperament, emotion, and cognition at fourteen months: the MacArthur Longitudinal Twin Study. 200 pairs of twins were assessed at 14 months of age in the laboratory and home. Measures were obtained of temperament, emotion, and cognition/language. Comparisons between identical and fraternal twin correlations suggest that individual differences are due in part to heritable influences. For temperament, genetic influence was significant for behavioral observations of inhibition to the unfamiliar, tester ratings of activity, and parental ratings of temperament. For emotion, significant genetic influence was found for empathy and parental ratings of negative emotion. The estimate of heritability for parental report of expression of negative emotions was relatively high, whereas that for expression of positive emotions was low, a finding consistent with previous research. For cognition and language, genetic influence was significant for behavioral indices of spatial memory, categorization, and word comprehension. Shared rearing environment appears influential for parental reports of language and for positive emotions, but not for other measures of emotion or for temperament.


The relations among infant temperament, security of attachment, and behavioral inhibition at twenty-four months. The purpose of this study was to examine the relations among infant temperament, attachment, and behavioral inhibition. 52 infants were seen at 2 days, 5, 14, and 24 months of age. Assessments were made of temperament at 2 days and 5 months of age, and attachment and behavioral inhibition were assessed at 14 and 24 months, respectively. EKG was recorded at each assessment, and measures of heart period and vagal tone were computed. Distress to pacifier withdrawal at 2 days of age was related to insecure attachment at 14 months. 2 types of distress reactivity at 5 months, reactivity to frustration and reactivity to novelty, were identified and related to high vagal tone. Attachment classification at 14 months was directly related to inhibited behavior at 24 months. Infants classified as insecure/resistant were more inhibited than those classified as insecure/avoidant. In addition, an interaction of infant reactivity to frustration and attachment classification was found to predict inhibition at 24 months. Infants classified as insecure/resistant and who had not cried to the arm restraint procedure at 5 months were the most inhibited at 24 months. These findings are discussed in terms of hypotheses regarding multiple modes of distress reactivity and regulation in early infancy and their different social and behavioral outcomes.


Psychophysiology in attachment interviews: converging evidence for deactivating strategies. By asking the subject to consider a host of potentially threatening attachment-related issues, the Adult Attachment Interview (AAI) allows an assessment of different strategies for regulating the attachment system. These strategies can be assessed along the 2 dimensions of security/anxiety and deactivation/hyperactivation. The greatest inferential leaps may be in characterizing strategies as deactivating. For example, individuals using deactivating strategies often report extremely positive relationships with parents, display restricted recall of attachment memories, and play down the significance of early attachment experiences. If these descriptive features are guided by a strategy that requires diverting attention from attachment information, subjects employing this strategy should experience conflict or inhibition during the Attachment Interview. In the present study, skin conductance levels were monitored for 50 college students during a baseline period and throughout the Attachment Interview. Subjects employing deactivating strategies showed marked increases in skin conductance levels from baseline to questions asking them to recall experiences of separation, rejection, and threat from parents. This finding supports the notion that individuals employing deactivating attachment strategies experience conflict or inhibition during the Attachment Interview.


Reliability and validity of behavior problem checklists as measures of stable traits in low birth weight, premature preschoolers. Mothers, teachers, and assistant teachers completed the Richman Behavior Checklist (BCL) at ages 2 and 3 years and the Achenbach Child Behavior Checklist for Ages 2-3 (CBCL 2-3) at 3 years for a large sample of low birth weight, premature children. Interinstrument correlations for total scores were moderate, higher for teachers and assistant teachers than for mothers, with moderate temporal stability for BCL scores. Interrater agreement for either total scores or classifications of clinically significant scores was moderately high between teachers and assistant teachers only, and children identified as disturbed by mothers versus teachers represent almost nonoverlapping groups. Furthermore, many more children were identified as disturbed using the BCL. The most powerful predictors of mothers' total CBCL 2-3 scores were HOME Inventory scores and self-reported depression. The use of these scales in clinical and research contexts is discussed.


Maturation of human fetal responses to vibroacoustic stimulation. Maturation of human fetal response to vibroacoustic stimulation was examined in 60 fetuses from 23 to 36 weeks gestational age. Subjects received vibroacoustic or no-stimulus control trials (randomly assigned) while fetal heart rate (FHR) was recorded and movement was observed on real-time ultrasound scan. Initially, at 26-28 weeks, a small FHR deceleration response occurred; subsequently, FHR acceleration responses occurred. From 29 weeks, 83%-100% of subjects responded with an FHR acceleration > or = 10 BPM on the first vibrator trial and accelerations were observed on 83%-92% of all vibrator trials. From 26 to 36 weeks the percentage of fetuses responding with movement on the first vibrator trial increased from 58% to 100%; on all vibrator trials responses increased from 53% to 94%. It was concluded that maturation of human fetal response to vibroacoustic stimulation begins at about 26 weeks gestation, increases steadily over a 6-week period, and reaches maturity at about 32 weeks.


Adult tactile stimulation during face-to-face interactions modulates five-month-olds' affect and attention. 3 studies were designed to investigate infant responses to tactile stimulation during brief adult-infant interaction using a modified still-face (SF) procedure. When adults pose a neutral SF expression, infants decrease gazing and smiling at the adults, and some increase grimacing, relative to normal interaction periods. This SF effect was substantially reduced in Study 1 when mothers or strangers continued to touch infants during the SF period. In Studies 2 and 3, tactile versus visual and active versus passive aspects of adult touch were isolated during different SF periods. Visible, active adult hands unaccompanied by touch elicited infant attention, but not smiling, during the SF period. By contrast, active, not passive, adult touch substantially reduced the SF effect, even when the adult's hands were invisible. In the latter condition, infants continued to gaze and smile at the adult's SF. Thus, adult facial expressions are not the only modulator of infant affect and attention during social exchanges; adult touch appears to play an active role.


Developmental change in infant categorization: the perception of correlations among facial features. Previous studies indicated that the ability to detect correlations among attributes emerges between 7 and 10 months of age. In the present study, the generality of this developmental transition was examined. Using an infant-control habituation procedure, 48 7- and 10-month-old infants were tested for the perception of correlations among basic facial features. The developmental effects were replicated. Only the 10-month-old infants demonstrated their sensitivity to the pattern of correlation by generalizing to a novel face that preserved the experienced pattern of correlation, while showing increased attention to a face in which the pattern of correlation was violated. 7-month-old infants generalized to both test stimuli containing familiar features, regardless of the status of the correlation. Implications for face perception and the processing of categorical information are discussed.


On wooden pillows: multiple classification and children's category-based inductions. Previous research has indicated that preschoolers do not distinguish between properties that are generalizable within a given category and those that are not. 2 possible general constraints on children's cognition are proposed to account for these findings. 3 studies are reported that argue against the presence of such general constraints. We examine preschoolers' understanding of the properties associated with material (e.g., wood, cotton) and object (e.g., chair, pillow) categories. In Study 1, subjects consistently made inductions based on the material compositions of items when asked to predict texture and fragility. In Study 2, the same subjects judged that items that shared material would share an unfamiliar dispositional property (e.g., gets sodden in water), but items that shared object kind would share a novel functional property (e.g., used for accelerating). Study 3 tested a younger sample of 3-year-olds and found the same sensitivity to category type, albeit with larger individual differences. By age 3, children use different modes of categorization to generalize different kinds of phenomena. These results argue against general limitations on children's abilities to use categories to make inductions. Even when children lack specific theoretical knowledge, the ability to organize phenomena into domains allows children to recognize which categories are relevant in different situations. This understanding can provide a basis for the development of more specific theories.


Comparison of the attachment rates of males of the ticks Amblyomma hebraeum and A. variegatum to cattle, sheep and rabbits in the absence of aggregation-attachment pheromone. Losses in domestic ruminants caused by heartwater (Cowdria ruminantium infection) in Zimbabwe and Mozambique are greater when the vector is Amblyomma hebraeum than when the vector is A. variegatum. It has been suggested that the epidemiology of the disease may be influenced by the rates at which unfed adults of these two tick species attach to uninfested hosts (i.e. in the absence of the male-produced aggregation-attachment pheromone [AAP]). In this study we confined unfed males of A. hebraeum and A. variegatum on uninfested cattle, sheep and rabbits and recorded their attachment rates. Males of both species attached more rapidly on cattle than on sheep or rabbits. Males of A. hebraeum attached more rapidly than males of A. variegatum on all three host species. The differences in the attachment rates between the two species were much greater on sheep and rabbits than on cattle. The findings suggest that in the absence of AAP, pioneer males of both tick species may attach to cattle, and pioneer males of A. hebraeum may also attach to sheep. The differences in the attachment rates of A. hebraeum and A. variegatum provide a possible explanation for observed differences in the epidemiology of heartwater associated with these two vector species.


The effects of nutritional status of rabbits and sheep on their resistance to the ticks Rhipicephalus evertsi evertsi and R. appendiculatus. Rabbits and sheep were exposed to low- and high-protein diets and subsequently infested three times with adults of Rhipicephalus appendiculatus and Rhipicephalus evertsi evertsi. The mean weight of R.e. evertsi females which dropped from rabbits maintained on a high-protein diet decreased from 515.0 +/- 24.9 mg (naive) to 381.5 +/- 25.0 (second infestation) to 340.3 +/- 23.3 mg (third infestation) while the weight of ticks fed on animals which were exposed to a low-protein diet did not change significantly (2.7%). The mean weight of engorged females of R. appendiculatus which completed their blood meal on rabbits (high protein) decreased from 520.9 +/- 31.8 (naive) to 369.3 +/- 39 mg (3rd infestation), a significant decrease of 29.1% compared to a 12.3% decrease in weight between the 1st and 3rd infestation of females fed on animals on a low-protein diet. Rhipicephalus e. evertsi fed on sheep exhibited the same phenomenon. The mean decrease in weight of 4rd-infestation ticks which dropped from sheep fed lucerne was 26.2% compared to 16.6% for ticks from sheep which were fed on grass. Hosts maintained on a low-protein diet failed to acquire resistance to ticks, lost weight and developed anaemia while those on a high-protein diet developed resistance, maintained weight and did not develop anaemia. The nutritional stress of the hosts and its application in South Africa are discussed.


The identification of a shared immunogen present in the salivary glands and gut of ixodid and argasid ticks. The identification of a 70-kDa immunogen present in salivary gland extracts of several ixodid species, namely Hyalomma truncatum (sweating-sickness-inducing (SS+) and non-inducing (SS-) strains), Hyalomma marginatum rufipes and Rhipicephalus evertsi evertsi, is reported. The immunogen was identified by Western blots using a monoclonal antibody of the IgM isotype directed against a 70-kDa immunogen present in the salivary glands of (SS-) female H. truncatum ticks. Cross-reactivity with the gut of unfed adult ixodid ticks, Amblyomma hebraeum, Rhipicephalus simus simus, R. evertsi evertsi, Rhipicentor nuttali, H.m. rufipes, and salivary glands of adult argasid species, Ornithodoros savignyi and Ornithodoros moubata, was demonstrated using ELISA.


Abnormal molecular weight profile of urinary protein in rats with streptozotocin-induced diabetes. A quantitative analysis of the molecular weight (MW) profile of urinary protein by SDS-PAGE was performed in streptozotocin (STZ)-injected, non-ketotic diabetic rats (DM group), diabetic rats receiving dipyridamole (DM-DIP group), normal rats (C group) and STZ-injected rats with near-normal glycemia due to insulin treatment (DM-INSULIN group). In the DM group, decrease of a small MW protein (SMWP) (MW 19.5 k) was found at 2.5 weeks, and an increase of larger MW proteins (LMWP) (MW 68 [albumin], 55 and 29 k) together with a decrease of SMWPs (MW 19.5 and 15 k) was found at 15 weeks, as compared to the C group: the MW profile of urinary protein in the DM-INSULIN and C groups was indistinguishable. At 15 weeks, creatinine clearance (Ccr) was significantly depressed and an increase in the mesangial matrix with electron dense deposits was evident in the DM group. The urinary protein abnormalities were partially corrected and the reduction of Ccr was absent in the DM-DIP group with no effect on glomerular morphology. STZ-induced diabetes in rats is accompanied by a reduction of urinary SMWP, and a subsequent increase of LMWP and depression of Ccr: dipyridamole ameliorates urinary protein abnormalities and prevents the reduction of Ccr.


Delayed onset and decreased incidence of diabetes in BB rats fed free radical scavengers. We tested the hypothesis that free radicals play a role in the selective destruction of pancreatic beta-cells in BB/Wor rats. Diabetes-prone BB rats of both sexes and 40 days of age were divided into three groups. The control group was fed ad libitum Purina rat chow powder, while the experimental group was fed ad libitum the rat chow powder blended with a mixture of four known free radical scavengers: allopurinol, mercaptopropionylglycine, dimethylthiourea and Vitamin E. A third group was pair-fed 10 g chow powder/rat/day, since in earlier experiments we observed that rats on the experimental diet consumed only about 10 g/rat/day. All rats were studied up to age 120 days. Body weight and food intake were measured daily. Urine was tested for glucose beginning at age 60 days. When glucosuria appeared, blood glucose and urinary ketones were measured. Body weight gain in the experimental and pair-fed groups was similar, but lower than the control group. Life table analysis of the data showed a decreased and a delayed onset of diabetes in the rats fed free radical scavengers. Thus, the results of this study demonstrated that calorie restriction and the related impaired growth did not affect the incidence of diabetes in the BB rat. In addition, the results suggested a role for free radicals in the spontaneous destruction of pancreatic beta-cells in the BB rat.


Presence of autoimmunity to pancreatic antigens in a patient with fibrocalculous pancreatic diabetes. A case of fibrocalculous pancreatic diabetes (FCPD) is reported for which antibody and cellular immune characteristics were determined. The patient, a Thai woman, had serum islet cell antibodies (ICA) that were detected by both immunoperoxidase staining and an indirect enzyme-linked immunosorbent assay (ELISA). Serum anti-human insulin antibodies were negative by a displacement ELISA. Lymphoproliferation assay against pancreatic antigen prepared from a blood group O cadaveric donor was positive. Increased CD8+ lymphocytes were observed using direct immunofluorescence staining and flow cytometry. CD4+ T lymphocytes, B lymphocytes and NK cells were within normal levels. These findings provide evidence for autoimmunity to pancreatic antigens in a patient with fibrocalculous pancreatic diabetes.


Effects of the combination of insulin and gliclazide compared with insulin alone in type 2 diabetic patients with secondary failure to oral hypoglycemic agents. Twenty non-insulin-dependent diabetic patients on insulin therapy for more than 2 months due to secondary failure to oral hypoglycemic agents (OHA) were additionally treated with gliclazide, 80 mg b.i.d., for 1 month and 160 mg b.i.d. for a further 2 months, while reducing insulin dose gradually according to glycemic control. At the end of the first month, fasting blood glucose had decreased from 12.8 +/- 0.7 to 9 +/- 0.8 mM (mean +/- standard error; P < 0.005) and thereafter remained stable. Insulin requirements decreased from 34.2 +/- 2.5 to 18.3 +/- 3.2 U/day (P < 0.001). Three patients were able to cease insulin treatment altogether. A direct correlation was found between final insulin dose and previous duration of infusion monotherapy (r = 0.52; P < 0.05). C-peptide/glucose score (fasting C-peptide/fasting BG x 100) increased from 0.11 +/- 0.03 to 0.21 +/- 0.05 (P < 0.05). We conclude that combined therapy reduces insulin requirement by increasing endogenous secretion, which may mainly affect hepatic glucose production as indicated by greater improvement in fasting vs. post-prandial blood glucose. This therapy could avoid hyperinsulinemia, which has been reported to be involved in macrovascular complications, and the additional haemovascular properties of gliclazide could make it more effective in such a combination.


The association between clinical risk factors and outcome of diabetic foot ulcers. The aim of the study was to describe the association between clinical risk factors in diabetic patients with food ulcers in relation to outcome. A prospective study of 314 consecutively presenting diabetic patients with foot ulcers referred to the Department of Internal Medicine between July 1, 1983 and June 30, 1987. All patients were followed to final outcome. All patients were treated by the same multi-disciplinary foot care team at the Department of Medicine, both as in- and out-patients. Healing was defined as intact skin for at least 6 months. One hundred and ninety-seven patients healed primarily, 77 after amputation, and 40 died unhealed. Signs of macroangiopathy were more common among patients who healed after amputation. The outcome was strongly related to age, though 43% of the patients with an age over 80 years healed primarily. There was no difference in smoking habits between patients who healed primarily and those who required amputation to heal. Diabetic nephropathy was found in 26% of the patients and was strongly associated with amputation. Presence of retinopathy was found in 54% of the patients, but this finding was not related to the outcome. There were no differences in short-term metabolic control as assessed by hemoglobin A1c levels between patients who healed primarily and those who healed after amputation. The presence of diabetic foot ulcers was strongly associated with age and diabetic complications such as multiple cardiovascular disease and nephropathy, which were important factors related to amputation.


Outcome of gestational diabetes in Bengali Asians living in an east London health district. The characteristics and outcome of pregnancy complicated by gestational glucose intolerance are described in a consecutive series of 69 Bengali Asian patients and a parallel group of 22 Caucasian patients. The Bengali patients were older and of higher parity than the Caucasians and more frequently required insulin therapy. However, the outcome of pregnancy was similar in terms of antenatal clinic attendance, the number of antenatal hospital admissions, glycaemic control, birthweight and mode of delivery. Of those patients who attended for postnatal glucose tolerance test, 20% of the Bengali population demonstrated persisting abnormality of glucose tolerance, whereas no abnormalities were evident in the Caucasian group. These findings are consistent with the high prevalence and early age of onset of non-insulin-dependent diabetes in Asian populations. The World Health Organisation (WHO) criteria for the diagnosis of impaired glucose tolerance proved insufficiently sensitive for the diagnosis of gestational diabetes. This was particularly demonstrated by four patients with apparently normal glucose tolerance by WHO criteria who subsequently required insulin therapy.


Effect of disease duration on cardiac autonomic reflexes in young patients with insulin-dependent diabetes mellitus. The association of disease duration with deterioration of cardiovascular autonomic reflexes was studied in two groups of young patients with insulin-dependent diabetes mellitus (IDDM). The mean age of the patients in both groups was 31 years and the mean duration of the disease was 3 (n = 18) and 16 (n = 22) years. No significant difference in group means was seen in the test parameters of autonomic nerve function. However, five patients with long-term disease, but none with short-term disease, had test scores indicating cardiac autonomic neuropathy. It was concluded that (1) the duration of the disease has no overall effect on autonomic nerve function in young patients with IDDM, but (2) a few individuals with IDDM may have some precipitating factors leading to autonomic neuropathy in the course of the disease.


Automatic detection and measurement of EMG silent periods in masticatory muscles during chewing in man. Silent periods are transient stops of muscle activity that are induced by mechanical or electrical stimulus. The current report describes a new algorithm which enables automatic detection and measurement of silent periods that occur in the EMG of human masticatory muscles during chewing efforts together with jaw positions in space at the occurrence of the silent periods. The EMG signal for detection of the silent period is modeled based on the observation of the EMG records induced from the jaw-closing muscles during chewing efforts in seven volunteer subjects. The algorithm for automatic detection and measurement of the EMG silent period has been applied successfully to real EMG data and the performance of the software was confirmed to be sufficiently reliable. The results of the analysis are stored in a biosignal database for possible clinical use.


Subclinical neuropathy in children with inherited haemostasis disorders. Motor and sensory conduction of the right peroneal and sural nerves was studied in 28 children (17 HIV seropositive) with inherited hemostasis disorders, without any symptoms of neuropathy. The amplitude ratio of the evoked muscle potential (EMP) at distal stimulation to that at proximal stimulation at the right peroneal nerve was also studied. Thirty healthy aged-matched children were used as controls. There was no statistically significant difference in the distal latency, amplitude and conduction velocity of motor and sensory nerves between patients and controls. On the contrary, a great diminution of amplitude of the EMP during proximal stimulation of nerve was observed in patients, statistically very significant, as compared to controls. This difference was independent of patients' age, severity of hemostasis defect or HIV status. In 9 patients the amplitude was within normal limits. Intraneural oozing due to trivial trauma is postulated as a possible mechanism of peroneal nerve lesion.


Inadequacy of transcranial magnetic stimulation in the neurophysiologic assessment of Bell's palsy. Transcranial magnetic stimulation is a non-invasive procedure which to stimulate the brain cortex and the peripheral nerve pathways. A new technique was recently introduced to record the muscle action potential of facial muscles by means of transcranial magnetic stimulation of the facial nerve. The experimental data that was obtained indicate that this technique allows to stimulate the facial nerve above the stylomastoid foramen: a greater tract of the nerve can therefore be explored than what was possible with the traditional electrical stimulation at the mastoid. Until now no comparison data was available on the clinical usefulness of the two methods. We decided to study 14 normal controls and 26 patients suffering from unilateral idiopathic facial palsy (Bell's palsy) and to submit these two groups to magnetic transcranial stimulation and electrical stimulation of the facial nerve in the mastoid region, to the purpose of observing where the nerve is stimulated by the magnetic impulse and which of the two techniques can be of accurate prognostic value in the study of the evolution of the clinical lesion. The electromyographic responses were elicited by the electrical stimulation at the mastoid and by transcranial stimulation after positioning the coil on the parieto-occipital scalp. A recording was taken from the ipsilateral orhicularis oculi muscle utilising two cupped electrodes. The latency and the amplitude of the compound muscle action potential were measured bilaterally in order to compare the results obtained on both the affected and the healthy sides. The patients were scheduled to two neurophysiological and clinical evaluations at about 30 days interval one from the other: the first test was not carried out before 20 days from the onset of the deficit; further clinical examination was carried out only 6 months later. The analysis of the results obtained in the normal controls submitted to transcranial magnetic stimulation indicate that the nerve is activated at the point where it originates from the brainstem. The study carried out showed that transcranial magnetic stimulation of the facial nerve, does not provide data which can be correlated to the clinical situation observed at the time of the study; furthermore, transcranial magnetic stimulation does not supply any prognostic data on the clinical evolution of the lesion.


CTSS: an interactive microcomputer program for the clinical screening of carpal tunnel syndrome. II. Statistical and computational aspects. Details of the development and testing of a microcomputer-based statistical decision aid for screening carpal tunnel syndrome are given. The clinical and operational details have been reported in (14).


Cognition in homozygous beta-thalassemia disease: a multichannel auditory event-related potential (P300) study. Auditory Event-Related Potentials (AERP) were elicited in 25 beta-thalassemic patients, three days before and three days after a blood transfusion. The amplitude, latency and topographic distribution of P300 (P3) as well as N1, P2, N2 components were measured for the two assessment times. No significant differences in either amplitude, latency or topography were observed between the two situations, but thalassemic patients had significantly prolonged P3 latencies comparing to controls though none of them exceeded 3 standard deviations of the control mean values. Regarding P3 topography, 10 out of 25 patients showed a right centroparietal distribution area. It is concluded that information processing, as far as it is reflected in AERP components is impaired in thalassemic patients and blood transfusion have no significant influence in cognitive functions.


Muscle conduction velocity and morphology after prolonged hypoxemia and diabetes in rats. One of the electrophysiological abnormalities in the experimental rat model of chronic hypoxia (10% O2) and in the experimental rat model of diabetes is an increase in jitter in the stimulated single fibre EMG, which is thought to result from a primary disorder of the axon with its terminal branches. But muscle fibre alterations that influence the propagation of muscle action potentials can also increase jitter. The contribution of possible changes in muscle conduction velocity and muscle morphology to jitter were investigated in the present study. Muscle conduction velocities were determined and compared with the morphological properties of muscle fibers in muscles of control, chronic hypoxic and terminal-stage diabetic rats. The mean muscle conduction velocities were in the same range in the three groups. The muscle fibre type composition and the mean muscle fibre diameters were about the same in the hypoxic and the control rats, whereas the muscles of the diabetic rats showed a higher percentage of intermediate type muscle fibres, which is suggestive of muscle degeneration, and a smaller mean muscle fibre diameter in comparison with muscles of the hypoxic and the control rats. It is concluded that the similarities between the electrophysiological properties of the muscles despite differences in their morphology, indicate that there is primary axonal degeneration in diabetic hypoxic rats.


Tumor necrosis factor-alpha induces clustering in ovarian theca-interstitial cells in vitro. Tumor necrosis factor-alpha (TNF) has been implicated in the regulation of steroidogenesis in theca-interstitial cells (TIC). The purpose of this study was to evaluate any change in TIC morphology during the time course of TNF-induced inhibition of LH-stimulated androstenedione production. Ovaries from immature hypophysectomized rats were enzymatically digested and highly purified TIC were obtained by density gradient centrifugation. TIC treated with TNF (0.1-10 ng/ml) demonstrated distinct clustering in the presence and absence of LH (50 ng/ml). The number of clusters and the mean area per cluster were greatest after 4 days as a result of treatment with 1 or 10 ng TNF/ml. In addition, a dose-dependent inhibition of LH-supported androstenedione production was induced by TNF. TNF also inhibited LH-induced androstenedione in TIC after 2, 4, or 6 days of continuous LH treatment, and TIC clustering still occurred. TIC clustering was impeded by the protein kinase inhibitor H7 at 10 microM; however, the protein kinase inhibitor, HA 1004 (5 microM), did not inhibit TNF-induced clustering in TIC. Since H7 blocked TNF induced clustering, but did not block TNF inhibition of LH stimulated androstenedione synthesis, it is suggested that alternate signal transduction pathways for TNF induced inhibition of LH-stimulated androstenedione and stimulation of clustering of TIC may exist. The results also indicate that the TNF-induced TIC clustering may be independent of the TNF-induced inhibition of LH-stimulated androstenedione production and states of LH-induced differentiation of TIC.


Electrophysiological findings in poliomyelitis patients at the subacute phase. Electrodiagnostic tests-needle EMG, nerve conduction and somatosentory evoked potential (SEP) studies of the upper and the lower limbs were performed in three patients during the subacute phase of poliomyelitis. Although poliomyelitis is traditionally considered a "pure motor" disease, involvement of the sensory system was demonstrated by prolonged sensory nerve conduction and by delayed latencies and amplitude asymmetries of SEPs obtained from the lower limbs. Sensory deficit in poliomyelitis is well known to exist during the acute phase of illness. The present report describes the electrophysiological findings in patients during the subacute phase, several months after onset of illness. Sensory nerve action potentials and sensory evoked potentials were abnormal, especially those elicited by lower limb stimulation although the patients had no overt signs of sensory loss at that time. The associated EMG findings are described, and the probable pathologic changes of the motor unit are discussed.


Enhanced stimulation of follicle maturation and ovulatory potential by long acting follicle-stimulating hormone agonists with extended carboxyl-terminal peptides. The induction of granulosa cell differentiation and follicle maturation is dependent upon the stimulatory actions of FSH. Our recent studies used recombinant DNA technology to fuse the carboxyl-terminal peptide (CTP) of hCG beta-subunit to the carboxyl-terminus of the FSH beta-subunit. The resulting FSH analog has identical in vitro receptor-binding and biological activities as wild-type FSH (WT-FSH), but an increased circulating half-life. The present studies examined further the ability of FSH with one (FSH-CTP1) or two (FSH-CTP2) appended CTPs to promote granulosa cell differentiation and follicle ovulatory potential. WT-FSH, FSH-CTP1, and FSH-CTP2 were produced from Chinese hamster ovary cells transfected with the common alpha-subunit and respective beta-subunit. Hormone concentrations were quantitated by RIA, and relative levels confirmed by radioligand receptor assay. Both FSH-CTP1 and FSH-CTP2 retained full FSH receptor-binding activity, but did not bind LH receptors. To compare in vivo bioactivity, immature estrogen-primed female rats received ip injections of FSH or the agonists at 0 and 24 h. At 48 h, substantial stimulation (up to 2.5-fold) of ovarian weight was induced by 1.0 and 3.0 IU/day FSH-CTP1 or FSH-CTP2, whereas a higher dose (10 IU/day) of WT-FSH was required for an 1.8-fold stimulation. Although the in vivo potencies of FSH-CTP1 and FSH-CTP2 were similar, FSH-CTPs were about 10-fold more potent than WT-FSH in inducing granulosa cell aromatase activity and LH receptors. We further reduced the frequency of hormone administration. Increasing doses (1-10 IU) of a single ip injection of FSH-CTP1 resulted in dose-dependent increases in granulosa cell aromatase activity and LH receptor content 48 h later. Although a single injection (10 IU) of WT-FSH had no effect, the same total dose of WT-FSH administered as four 2.5-IU injections 12 h apart was effective. To test the ovulatory potential of ovarian follicles, rats received a single injection of FSH-CTP1, followed 52 h later by 5 IU hCG to induce ovulation. Although hCG did not induce ovulation in females receiving a single dose (10 IU) of WT-FSH, 20 +/- 2 and 43 +/- 5 ovulated ova/rat were found in animals primed with 3 and 10 IU FSH-CTP1, respectively. Because twice daily injections of WT-FSH (2.5 IU/injection) also increased the ovulatory potential of the ovary, the enhanced effectiveness of FSH-CTP1 appears to be related to its increased circulating half-life.(ABSTRACT TRUNCATED AT 400 WORDS)


Some conceptual remarks about supraspinal mechanisms in the control of voluntary and reflex motor activities. The present paper analyses the supraspinal control of motor functions and sensorimotor integrations. Attention was paid mainly to three phenomena involved in these mechanisms: the Bereitschaftspotential, the long latency reflex responses and the short latency somatosensory evoked potentials (SEPs). The study includes the problems of long loop motor control and dyscontrol, the gating process of SEPs by movement, the role of N18 component of SEP and the analysis of supraspinal modulation of the H-reflex excitability curve in healthy subjects and in patients with some cerebral dysfunction. It was found that the amplitude of the Bereitschaftspotential increased with peripheral nerve stimulation. The experiments have shown a positive relationship between the long latency reflex latencies and the distance of the corresponding muscle from the brain. The amplitude of the long latency reflex response was found to be higher and its synchronization better in phasic movements than in a slightly sustained contraction. The short latency somatosensory evoked potentials were distinctly attenuated by movement gating. By its wide spread negativity, the N18 component probably facilitates the cortical transfer of the long latency muscle response. The H-reflex excitability curves in patients with various cerebral dysfunction exhibited a characteristic course corresponding approximately to the degree of dysfunction in focal cerebral lesions, arterial hypertension and neurasthenias.


A radioimmunoassay of rat type I iodothyronine 5'-monodeiodinase. A highly sensitive, specific, and reproducible RIA has been developed to measure rat type I iodothyronine 5'-monodeiodinase (5'-MD). A 16-amino acid peptide (LAP-744) corresponding to a portion of the carboxy-terminal region of the rat liver 5'-MD, as predicted from its cDNA, was synthesized, and rabbits were immunized with the peptide-BSA conjugate. In a final dilution of 1:15,000, our anti-5'-MD antibody bound about 30-35% of a tracer amount of [125I]LAP-744. The detection threshold of the RIA approximated 0.08 pmol LAP-744 or an equivalent amount of 0.08 pmol 5'-MD. Rat liver and kidney microsomes produced dose-response curves that were essentially parallel to that of LAP-744. No inhibition of binding of [125I]LAP-744 to antibody was produced by 0.3 mg or less rat microsomal proteins from testes, heart, brain, muscle, spleen, intestine, lung, placenta, or fetal liver. Recovery of nonradioactive LAP-744 added to spleen microsomes averaged 103%. The coefficient of variation averaged 4% within an assay and 11% between assays. In 16 normal rats studied, the mean (+/- SD) 5'-MD content was 2.4 +/- 0.22 pmol/mg protein in liver microsomes and 2.5 +/- 0.27 pmol/mg protein in kidney microsomes. Fasting of the rat for 2-4 days was associated with a significant reduction in both the activity and the content of the 5'-MD in liver and kidney. Hypothyroidism was also associated with a significant decrease in the activity and content of 5'-MD in both tissues. Significant opposite changes were observed in these parameters in hyperthyroidism. Treatment of the rat with sodium ipodate for 3 days was associated with a significant decrease in both the activity and the content of 5'-MD in liver and kidney. A similar treatment of the rat with propylthiouracil induced a clear reduction in the activity of 5'-MD in liver and kidney, but the content of the enzyme was significantly increased in both tissues. Rats treated with aurothioglucose for 3 days exhibited a significant decrease in 5'-MD activity in liver and kidney microsomes, whereas the tissue content of 5'-MD was not affected. A similar treatment of the rat with methimazole had no significant effect on either the activity or the content of 5'-MD.(ABSTRACT TRUNCATED AT 400 WORDS)


Complete ulnar innervation of the thenar muscles combined with normal sensory fibres in a subject with no peripheral nerve lesion. A complete ulnar innervation of all thenar muscles, including the opponens, have to our knowledge been described only in patients with severe traumatic lesions of the median nerve. The present study reports a subject with exclusive ulnar innervation of the thenar muscles in the right hand. The patient had no anamnestic or objective signs of peripheral nerve lesions. While his sensory and motor ulnar nerve fibres were normal, electrophysiological examination of the right median nerve showed normal course of the sensory fibres but apparently no motor fibres to the thenar muscles.


Distribution of cholecystokinin forms in intestinal secretory granule subtypes. Peptides and proteins destined to be released in response to stimuli are found in the regulated secretory pathway. Substances in this pathway are packaged into secretory granules, wherein they are often rendered osmotically inactive by complexing to an oppositely charged molecule. The complexing mechanism employed by members of the cholecystokinin (CCK) peptide family is unknown, but the heterogenous charges of CCK peptides makes it possible that different CCK peptides have different abilities to form intragranular complexes. If the number of osmotically active intragranular CCK peptides varies, corresponding variations in secretory granule density should result, and when intestinal CCK secretory granules were purified on isotonic density gradients, four granule peaks were observed. Granules containing greater proportions of short CCK forms tended to have the lowest buoyant densities, suggesting that they contain a greater number of osmotically active molecules than granules of lower density and that short or all intragranular CCK forms are osmotically active. CCK secretory granules also contained novel CCK forms; in addition to previously characterized forms, granules contained a CCK form that appears to be CCK-6 and a form that could arise from cleavage of CCK-58 at position 4, 10, or 12. Because intragranular enzymes are responsible for peptide posttranslational processing, the intragranular CCK forms observed in the present study are likely to be authentic CCK-processing products. Finally, CCK sorting in intestine apparently differs from that in a rat medullary thyroid carcinoma cell line, in which CCK-22 and CCK-33 are not found in the regulated secretory pathway.


The effects of acute training status on reliability of integrated electromyographic activity and "efficiency of electrical activity" during isometric contractions: a case study. "Efficiency of electrical activity" (EEA) is the measure of muscular force production per unit of neuromuscular electrical activity as measured by integrated electromyographic (IEMG) activity. To determine the effects of acute training status on day-to-day and within test reliability for both IEMG activity and EEA, one experienced weight trained male was observed on three separate days (age = 33 yrs., height = 172.7 cm, body weight = 81.4 kg). The first (I) and third (III) test days were preceded by 1-2 days rest from weight training, while the second test day (II) was preceded by 4 days of rest from weight training. Two external electrodes were placed on the right biceps brachii. EMG signals were rectified by an amplifier, while a signal gain of 5000 was utilized. Three different levels of isometric muscle activity using a dumbbell, were performed at 25.0 N (2.55 kg), 87.3 N (8.90 kg), and 157.9 N (15.90 kg) of force. These resistances represented 12%, 42% and 76% respectively, of the subject's maximum capabilities. Five trials were performed at each resistance on each of the test days. Repeated measures ANOVAs (3 x 3) were used to determine differences between test days and loads (p < or = 0.05). Within day variations were determined by coefficient of variation (CV = SD/mean x 100%). The EEA for each test day was curvilinear, with greater forces exhibiting lower EEA. Test day II exhibited the greatest EEA, which may have been related to the acute training status of the subject.(ABSTRACT TRUNCATED AT 250 WORDS)


Sympathetic skin response in spinal cord injured patients: preliminary report. Sympathetic skin responses (SSRs) were recorded in six spinal cord injured patients. These SSRs were obtained at hands and feet, after electrical stimulation of the median or the posterior tibial nerves. Below the level of the lesion, SSRs had similar latencies than normal subjects, but were more inconstant, with a lesser amplitude and elicited after stronger stimulus intensity. The origin of these somatosympathetic reflexes are discussed. SSRs recordings seem to be a simple and suitable technique for investigation of the autonomic nervous system of the spinal cord injured patients.


Reduction of alpha-naphthylisothiocyanate-induced hepatotoxicity by recombinant human hepatocyte growth factor. Hepatocyte growth factor (HGF) is a potent stimulator of DNA synthesis in cultured hepatocytes. To determine whether HGF has any activity in vivo, we have tested HGF in rats in which intrahepatic cholestasis was induced by acute administration of alpha-naphthylisothiocyanate (ANIT). The hepatotoxic effects of a single injection of ANIT were manifested 48 h later as large increases in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. These biochemical changes were accompanied by widespread periportal edema, hypertrophy of bile duct epithelium, and randomly scattered areas of liquifaction necrosis in the hepatic parenchyma. The increases in bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were markedly attenuated when HGF was administered 30 min before ANIT and again at 6, 12, 24, 30, and 36 h after ANIT. In addition, this HGF dosing regimen completely prevented the occurrence of parenchymal lesions, although it had no effect on periportal histopathology. The effect of ANIT was dose dependent; a maximal response was observed at 320 micrograms/kg per injection, with an intermediate response at 105 micrograms/kg. Delaying the administration of HGF until 12 h after ANIT was as effective as when administration was begun 30 min before ANIT. Taken together these results show that HGF can prevent some aspects of ANIT hepatotoxicity.


Paracrine regulation of adipose differentiation by arachidonate metabolites: prostaglandin F2 alpha inhibits early and late markers of differentiation in the adipogenic cell line 1246. The effect of arachidonate metabolites on the differentiation of the adipogenic cell line 1246 was investigated. Among the metabolites examined, only prostaglandin F2 alpha (PGF2 alpha) inhibited differentiation in a dose-dependent fashion with an ED50 of 3 x 10(-9) M. PGF2 alpha inhibited the mRNA expression of lipoprotein lipase, clone 154, and fatty acid-binding protein, which are early markers of differentiation, as well as glycerol-3-phosphate dehydrogenase specific activity and triglyceride accumulation, which are late markers of differentiation. Chronic exposure of 1246 cells to PGF2 alpha before and during differentiation indicated that the cells that have just initiated their differentiation program were the most susceptible to the inhibitory effect of PGF2 alpha. Since 1246 cells produce PGs, we determined whether the PG produced by the cells influenced adipose differentiation. Cyclooxygenase inhibitors added to the culture medium stimulated differentiation of 1246 cells up to 18-fold depending on the type and concentration of inhibitor used. In contrast, lipoxygenase inhibitors had no effect. Treatment of 1246 cells with arachidonic acid resulted in a dose-dependent inhibition of cell differentiation. Oleate or linoleate had no effect. These data indicate that PGF2 alpha inhibits early and late events of adipose differentiation and that the endogenous production of PGs (particularly PGF2 alpha) plays an important role as a negative paracrine or autocrine regulatory pathway of adipose differentiation.


Phorbol ester activation of the protein kinase C pathway inhibits gonadotropin-releasing hormone gene expression. The effects of the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C (PKC), and the PKC inhibitor staurosporine on GnRH secretion and mRNA levels were studied in GT1-7 hypothalamic neuronal cells. Dose-response and time-course studies revealed that TPA (10(-8) M) acutely increased GnRH secretion 3-fold at 3-6 h, which then declined to baseline at 24 h, while it progressively decreased GnRH mRNA levels by 50% and 70% at 6 and 24 h, respectively. To ensure that these effects were due to activation and not down-regulation of PKC, cells were treated for 30 min with TPA (10(-8) M). This brief exposure to TPA also resulted in a decrease (60%) in GnRH mRNA levels at 6 h, with a 1.5- to 2-fold increase in GnRH secretion compared to control values, suggesting that activation of PKC decreases the pretranslational expression of GnRH while increasing GnRH secretion. Additional studies measured PKC activity and documented a shift from a cytosolic to a membrane fraction after incubation with TPA, again supporting PKC activation. Exposure of GT1-7 cells to staurosporine (10(-8) M), a PKC inhibitor, resulted in no change in the level of GnRH mRNA or secretion at 6 h. However, incubation with both TPA and staurosporine prevented the decrease in GnRH mRNA levels and partially blocked the increase in GnRH secretion induced by TPA. We conclude that TPA, by activating the PKC pathway, acutely increases GnRH secretion, but dramatically decreases GnRH gene expression. The exact mechanism of these divergent effects on the synthesis and secretion of GnRH remain to be elucidated.


Ontogeny of hepatic nuclear triiodothyronine receptor isoforms in the rat. We have determined the contribution of the thyroid hormone receptor (TR) isoforms TR alpha 1 and TR beta 1 to the postnatal rise in rat hepatic nuclear T3-binding capacity. In agreement with previous studies, total hepatic nuclear binding capacity rose by about 8-fold from the 19th day of gestation to young adulthood at 2 months of age (0.10 +/- 0.03 to 0.86 +/- 0.17 pmol/mg DNA). The levels of specific TR species were measured by immunoprecipitation of T3-binding activity from hepatic extracts using a panel of antisera directed against specific regions of the TR isoforms. The difference between receptor immunoprecipitated with antibody against TR beta 1 and that precipitated with an antibody against an identical region in both TR beta 1 and TR alpha 1 was tentatively assumed to represent TR alpha 1. TR alpha 1 accounted for virtually all T3-binding activity in fetal liver on gestational day 19 (G19), increased by 2-fold shortly after birth, and remained constant thereafter. TR alpha 1 mRNA, on the other hand, was highest in concentration on G16 and fell by 50-75% in the adult. TR beta 1 was undetectable by immunoprecipitation of hepatic extracts from fetuses on G19. However, Northern analysis showed the presence of TR beta 1 mRNA in the fetal liver, which rose in concentration by 3- to 4-fold in late gestation and then remained constant. The contribution of TR beta 1 to total binding capacity rose to 33% and 40% on postnatal days 15 and 30, respectively, and to 80% in the adult liver. Immunohistochemical analyses of hepatic sections confirmed the presence of very low levels of TR beta 1 in fetal liver as early as G16 and G19, and a sharp rise in TR beta 1 protein concentration in the postnatal period. This indicated that the increase in TR beta 1-binding capacity results from increased TR beta 1 mass. The increase in TR beta 1-binding capacity, thus, is due to increased translational efficiency of the beta 1 mRNA or stabilization of the TR beta 1 protein. The prominence of TR alpha 1 in both rat fetal liver and fetal brain, as previously demonstrated in our laboratory, raises the possibility that this receptor isoform may carry out specialized functions in the fetus and that TR beta 1 subserves still other functions at later stages of development.(ABSTRACT TRUNCATED AT 400 WORDS)


Mouse uterine stromal cells secrete a 30-kilodalton protein in response to coculture with uterine epithelial cells. While uterine stromal cells (USC) appear to modify the function of uterine epithelial cells (UEC) under certain conditions in vivo, relatively little is known about the effect of epithelial cells on stromal cell differentiation and function. To determine if UEC modulate USC function in vitro, highly enriched (> 95%) cultures of polarized UEC were first cultured on Matrigel-coated filters in serum-free medium until confluent, then cocultured with USC for up to 120 h. Subsequently, while maintaining both cell types in physically separate compartments, filters containing UEC were removed, and USC phenotypic markers assayed. Coculture with UEC did not affect the expression of two markers of USC differentiation (desmin and laminin), USC DNA content, [35S]methionine uptake, or total protein synthesis or secretion. However, coculture of USC with UEC or medium conditioned by UEC induced the secretion of a 30-kilodalton protein (p30) from USC as early as 24 h of coculture and through 120 h of coculture. In addition, secretion of a 60-kilodalton protein by USC was frequently observed in response to coculture with UEC. Neither the hormonal stage from which uterine cells were recovered, nor the addition of exogenous progesterone or estradiol modulated UEC-induced p30 secretion. Several purified growth factors (transforming growth factor-beta, epidermal growth factor, interleukin-1 alpha, and fibroblast growth factor) added to the serum-free culture medium failed to induce p30 secretion by USC. The p30-inducing activity in UEC-conditioned medium could not be abolished by either heat or trypsin treatment, suggesting that it is not a protein. Purified prostaglandin E2 or F2 alpha or platelet-activating factor did not induce p30 secretion by isolated USC. Of several epithelial and fibroblastic cell lines tested, UEC and a human uterine adenocarcinoma cell line (RL95-2) were the most effective in inducing p30 secretion by USC. Moreover, UEC also were able to modulate protein secretion by nonuterine murine fibroblast cell lines. Collectively, these data demonstrate that UEC can modulate USC function in vitro via a soluble factor(s).


Pituitary extract causes aggregation and differentiation of rat mammary tumor MTW9/Pl cells. Alkaline pituitary extracts (PE) of the mammosomatotropic tumor MtTW10 differentiated cultured PRL-independent rat mammary tumor cells MTW9/Pl. Within 24 h, MTW9 cells growing in suspension began to aggregate and adhere to the plastic dish. Cultured dispersed MTW9 cells were undifferentiated, but PE treatment resulted in organoid aggregates that exhibited glandular luminal structures and periodic acid-Schiff-positive material consistent with basement membrane formation. Morphometric examination of organoids demonstrated a reduction in nuclear and cell perimeters compared to those of untreated cells. Electron microscopy showed that the treatment resulted in polarization, nuclear changes, junctional complexes, secretory spaces, microvilli, and basement membrane formation. A disaggregated undifferentiated tumor now appeared as a differentiated adenocarcinoma. PE induced expression of laminin and milk protein, but failed to increase fibronectin expression. Extracts of MTOM (a variant of MtTW10 which secretes little PRL) and bovine pituitary also produced aggregation and adhesion of MTW9. A number of tissue extracts, growth factors, and hormones failed to produce such aggregation. Laminin, but not fibronectin, produced aggregation and adhesion similar to those produced by PE. Cycloheximide inhibited the aggregation effect of PE, but not that of laminin. PE was mitogenic for MTW9, but inhibition of proliferation by vinblastine did not inhibit the aggregation induced by PE. These observations suggest that the pituitary contains a novel factor that stimulates matrix synthesis, resulting in differentiation, possibly laminin induced.


Specificity of steroid binding in New World primate B95-8 cells with a vitamin D-resistant phenotype. We recently described the existence of a competitive binding component in vitamin D-resistant New World primate cells that has a relatively low affinity (Kd, approximately 10(-8) M) but high capacity for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] compared to that possessed by the vitamin D receptor (VDR). Here we show that this binding component is capable of binding a vitamin D3 metabolite other than 1,25-(OH)2D3 as well as steroid hormones structurally disparate from vitamin D3 sterols. We studied the binding of [3H]1,25-(OH)2D3 and [3H]25-hydroxyvitamin D3 ([3H]25OHD3) in extracts of the vitamin D-resistant marmoset lymphoblastic cell line B95-8 in the presence and absence of potential competitive ligands, including 25OHD3, 1,25-(OH)2D3, 17 beta-estradiol, testosterone, and progesterone, at concentrations ranging from 1-100 nM. Compared to extracts containing the authentic VDR, extracts of B95-8 cells bound 180% more 1,25-(OH)2D3 and 12-fold more 25OHD3 on a weight basis. The affinity of this binder for 25OHD3 was 2.2 times as great as its affinity for 1,25-(OH)2D3. Further, at concentrations approaching the Kd of this binder for 1,25-(OH)2D3, 25OHD3 was 3 times more effective than 1,25-(OH)2D3 in competing with [3H]1,25-(OH)2D3 for binding. This binder eluted from a Sephadex G-100 column with an apparent mol wt of 58 kilodaltons, and pooled elution fractions from the column encompassing this mol wt range were capable of inhibiting binding of 1,25-(OH)2D3 to the VDR by 65%. Competitive steroid binding analyses showed estradiol to be at least as effective as 1,25-(OH)2D3 in inhibition of [3H]1,25-(OH)2D3 binding; homologous binding studies with 17 beta-estradiol as labeled and competitive ligand demonstrated that concentrations of the gonadal steroid that successfully displaced [3H]1,25-(OH)2D3 also displaced 17 beta-[3H] estradiol. Using [3H]25OHD3 as the labeled ligand and a more extensive array of competitive ligands, the rank order of steroid binding was 25OHD3 > 1,25-(OH)2D3 > or = estradiol = progesterone = testosterone. These results suggest that the phenotype of steroid hormone resistance in New World primates may result from the overexpression of an intracellular 58-kilodalton protein(s) that interferes with the steroid-receptor interaction by competing for ligand binding.


Analysis of pulsatile secretion of thyrotropin and growth hormone in the hypothyroid rat. To characterize the role of TRH in the generation of TSH pulsatility as well as the effect of hypothyroidism on episodic GH secretion, blood was constantly withdrawn (30-60 microliters/min) from rats treated with 0.02% methimazole in the drinking water for 8-10 days. This treatment significantly reduced circulating levels of both T3 and T4 and elevated plasma TSH; however, since thyroid hormone titers were still detectable (T3, 39.6 +/- 5.3 vs. 89.8 +/- 5.3 ng/dl in euthyroid animals), methimazole-treated rats were referred to as being mildly hypothyroid. TSH was found to be secreted in secretory bursts, consisting of one to several peaks in these rats. Pulsar analysis of TSH secretory profiles revealed a mean pulse frequency of 2.8 pulses/h, a mean pulse amplitude of 10 ng/pulse, and a mean pulse duration of 0.2 h. Euthyroid rats exhibited similar fluctuations of circulating TSH levels; however, due to the variability of the TSH RIA in the range of euthyroid TSH titers, no significant pulsatility was detected by Pulsar. Mean plasma TSH levels in eu- and hypothyroid rats were 2.3 +/- 0.3 and 14.6 +/- 1.8 ng/ml, respectively. To confirm that the TRH antiserum (TRH-AS) used in the present study for passive immunization had sufficient binding capacity to absorb endogenous TRH release, euthyroid rats were pretreated with either normal rabbit serum or TRH-AS, followed by the injection of clonidine (100 micrograms/kg BW, iv). This alpha 2-adrenergic agonist caused a significant (P < 0.01) 12.7-fold rise in plasma TSH levels in normal rabbit serum-treated animals, which was completely abolished by TRH-AS pretreatment, indicating that clonidine stimulates TSH secretion via activation of hypothalamic TRH release. When TRH-AS was slowly infused into hypothyroid rats that were sampled frequently for the detection of TSH pulsatility, it caused a significant (60.3%; P < 0.01) decrease in mean TSH levels, with TSH titers approaching euthyroid concentrations 1 h after the infusion of TRH-AS. The antiserum treatment also caused the disappearance of statistically significant (Pulsar) TSH secretory pulses. Mild hypothyroidism shifted the GH secretory profiles from a low frequency, high amplitude in euthyroid animals to a high frequency, low amplitude pattern in hypothyroid rats. Mean GH levels in hypothyroid rats were 76% lower than those in euthyroid controls. These findings show that TSH is secreted in a pulsatile fashion in the hypothyroid rat and that TRH is predominantly responsible for the generation of TSH pulsatility.(ABSTRACT TRUNCATED AT 400 WORDS)