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Establishment of ventral cell fates in the Drosophila embryonic ectoderm requires DER, the EGF receptor homolog.

The embryonic ectoderm in Drosophila displays a highly organized arrangement of specific structures along the dorsal-ventral axis. To establish this characteristic design, cells must receive instructive cues regarding their position. We present evidence that during stages 8-9 of embryonic development, the Drosophila EGF receptor homolog (DER) is essential for determining the identity of cells within the ventral ectoderm. In the absence of DER activity at this phase, alterations in cell fate are observed: Ventral cells acquire more dorsal fates, as visualized by the expression profile of specific markers. The ventralizing effect of DER appears to function later than that of the dorsalizing dpp pathway, and the spatial overlap between them is minimal. A model for the determination of cell fates along the dorsal-ventral axis involving the two pathways is presented. Some aspects of the mutant ectodermal and CNS phenotypes of the DER locus (faint little ball, flb) resemble the phenotype of mutations from the spitz group. Synergistic interactions between flb and spitz or Star mutations suggest that these genes participate in a common signaling pathway.

Animals↗

Dissociable contributions within the medial temporal lobe to encoding of object-location associations.

The crucial role of the medial temporal lobe (MTL) in episodic memory is well established. Although there is little doubt that its anatomical subregions-the hippocampus, peri-, entorhinal and parahippocampal cortex (PHC)-contribute differentially to mnemonic processes, their specific functions in episodic memory are under debate. Data from animal, human lesion, and neuroimaging studies suggest somewhat contradictory perspectives on this functional specialization: a general participation in declarative memory, an exclusive involvement in associative mnemonic processes, and a specific contribution to spatial memory are reported for the hippocampus, adjacent cortices, and the PHC. A functional lateralization in humans dependent on the verbalizability of the material is also discussed herein. To further elucidate the differential contributions of the various MTL subregions to encoding, we employed an object-location association memory paradigm. The memory for each of the studied associations was tested twice: by the object, and by the location serving as retrieval cue. The memory accuracy in response to both cue types was also assessed parametrically. Brain activity during encoding which leads to different degrees of subsequent memory accuracy under the two retrieval conditions was compared. We found the bilateral posterior PHC to participate in encoding of both the object associated with a location and the location associated with an object. In contrast, activity in an area in the left anterior PHC and the right anterior MTL was only correlated with the memory for the location associated with an object.

Adult↗

Effect of auditory cortex lesions on the discrimination of frequency-modulated tones in rats.

The lateralization of functions to individual hemispheres of the mammalian brain remains, with the exception of the human brain, unresolved. The aim of this work was to investigate the ability to discriminate between falling and rising frequency-modulated (FM) stimuli in rats with unilateral or bilateral lesions of the auditory cortex (AC). Using an avoidance conditioning procedure, thirsty rats were trained to drink in the presence of a rising FM tone and to stop drinking when a falling FM tone was presented. Rats with a lesion of the AC were able to learn to discriminate between rising and falling FM tones; however, they performed significantly worse than did control rats. A greater deficit in the ability to discriminate the direction of frequency modulation was observed in rats with a right or bilateral AC lesion. The discrimination performance (DP) in these rats was significantly worse than the DP in rats with a left AC lesion. Animals with a right or bilateral AC lesion improved their DP mainly by recognizing the pitch at the beginning of the stimuli. The lesioning of the AC in trained animals caused a significant decrease in DP, down to chance levels. Retraining resulted in a significant increase in DP in rats with a left AC lesion; animals with a right lesion improved only slightly. The results demonstrate a hemispheric asymmetry of the rat AC in the recognition of FM stimuli and indicate the dominance of the right AC in the discrimination of the direction of frequency modulation.

Acoustic Stimulation↗

Clinical implications of attachment concepts: retrospect and prospect.

The key features of attachment theory are summarized and the unresolved questions considered in terms of a behavioural control system, measurement of attachment security, qualities of attachment, the role of temperament, transformation of a dyadic quality into an individual characteristic, internal working models, manifestations of attachment post infancy, how one relationship affects another relationship, boundaries of attachment, associations with later functioning, the role of parenting qualities and patterns of caregiving, adaptive value of secure attachment, and disorders of attachment. The clinical implications are discussed in terms of: the need to reject the traditional psychoanalytic theories of development, the patterns of residential care for children, the provision of child care, the assessment of parenting, the effects of parental divorce and family break-up, "maternal bonding" to infants, psychotherapy and disorders of attachment.

Child↗

Hantaan virus infection with acute renal failure.

We report on 10 patients with acute renal involvement in Hantaan virus infection observed at the Department of Nephrology, Faculty of Medicine, Skopje, Republic of Macedonia, during a period of 3 years (October 1987-July 1990). Eight patients were male and 2 were female, aged 37.5 +/- 4.8 years. The diagnosis of Hantaan virus infection was proven by an indirect immunofluorescent and ELISA test with a significant increase of the titer after a week to ranges from 1:512 to 1:2,048. Percutaneous renal biopsy was performed in 3 cases using standard procedures for optical and immunofluorescent microscopy. Fever, weakness, headache, conjunctival injection, hematuria, and lumbar pain were clinical features all patients had in common. Complete anuria was noted in 7 out of 10 and oliguria in the other 3 of the 10 cases with serum levels of creatinine 967 +/- 152.6 mumol/L. Other following laboratory findings were leukocytosis in 10 out of 10 patients, with neutrophylia, and reduction of serum sodium and potassium in 8 out of 10, and a decrease in serum complement C3 in 3 out of 10 patients. Percutaneous renal biopsy confirmed interstitionephritis in 2 out of 3 biopsied patients and acute diffuse proliferative glomerulonephritis in the third. Interstitial mononuclear infiltration with dominant T cells proven with monoclonal antisera (direct immunoperoxidase method) was present in all 3 cases. The outcome of the disease was good in 8 of the 10 patients with a development of polyuric phase and complete recovery of renal function later. One patient with interstitial lesions on biopsy developed chronic renal failure, and the other with a concomitant brucellosis died during the polyuric phase of the disease.

Acute Kidney Injury↗

Outcome following occlusion of the middle cerebral artery.

Outcome was studied prospectively in 28 consecutive patients with occlusion of the middle cerebral artery (MCA). They comprise a subgroup of 101 consecutive patients with TIA or stroke less than or equal to 75 years of age, admitted within 72 h after the stroke. Cerebral angiography and CT-scan were performed within 1-2 days of admission. CT-scan was repeated 6 months later. Functional status on admission, 3 and 6 months after the stroke was evaluated using the Rankin disability scale (score 1-2: independent of others care, score 3-5: dependent on others care). The degree of hemiparesis was measured using the Medical Research Council's score. Thirteen had infarcts with a diameter less than or equal to 3 cm (mean 2.5 +/- 0.9 cm); 15 had infarcts greater than 3 cm (mean 6.3 +/- 1.4 cm); 10 had trunk occlusions; 18 had branch occlusions. MCA occlusions with large infarcts and severe hemiparesis on admission carried a poor outcome. Eleven (85%) of 13 patients with the case in only 1 (7%) of the 15 with infarcts greater than 3 cm, the remaining 14 (93%) had either died (40%) or were dependent (53%) (p less than 0.00005). Eleven (85%) of 13 patients with mild hemiparesis on admission were independent, while 13 (87%) of 15 with moderate or severe hemiparesis on admission had either died (40%) or were dependent on others' care (47%) 6 months after the stroke (p less than 0.0004). Type of occlusion (branch trunk) was a poor predictor of outcome.

Cerebral Arterial Diseases↗

Early growth and adult respiratory function in men and women followed from the fetal period to adulthood.

BACKGROUND: While some studies suggest that poor fetal growth rate, as indicated by lower birth weight, is associated with poor respiratory function in childhood, findings among adults remain inconsistent. A study was undertaken to determine the association between early growth and adult respiratory function. METHODS: A longitudinal birth cohort study was performed of 5390 men and women born full term and prospectively followed from the fetal period to adulthood. Weight at birth and infancy were recorded, and forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were assessed by standard spirometry at age 31 years. RESULTS: Adult FEV(1) and FVC increased linearly with higher birth weight in both men and women with no apparent threshold. After adjustment for sex, adult height and other potential confounders operating through the life course, every 500 g higher birth weight was associated with a higher FEV(1) of 53.1 ml (95% CI 38.4 to 67.7) and higher FVC of 52.5 ml (95% CI 35.5 to 69.4). These positive associations persisted across categories of smoking, physical activity and body mass index, with the lowest respiratory function noted among those with lower birth weight who were smokers, led a sedentary lifestyle or were overweight. Weight gain in infancy was also positively associated with adult lung function. CONCLUSION: Birth weight is continuously and independently associated with adult respiratory function. It is plausible that poor growth in early life may restrict normal lung growth and development, which could have long-term consequences on lung function later in life.

Adult↗

Long-term pressure-induced cardiac hypertrophy: capillary and mast cell proliferation.

To determine whether a prolonged duration of mechanical load on the ventricular myocardium leads to capillary proliferation, constriction of the pulmonary artery was produced in rats at 3 mo of age, and the hearts were examined 200 days later. Functionally, elevations of right ventricular systolic pressure, from 30 +/- 12 to 67 +/- 11 mmHg, and right ventricular end-diastolic pressure, from 2.4 +/- 1.4 to 8.6 +/- 2.4 mmHg, were found. Anatomically, a 69% enlargement in right ventricular mass was observed, and this hypertrophic growth was characterized by a 78% thickening of the wall with no change in ventricular wall area, the latter calculated from the quotient of ventricular volume and wall thickness. Morphometric data showed a 44% increase in the capillary-to-myocyte ratio, a 66% augmentation of the total length of capillaries in the whole ventricle, and a 77% greater number of capillaries across the ventricular wall. Furthermore, these indexes of neogenesis of capillary units were associated with a more than three fold increase in the numerical density of mast cell profiles in the myocardium. In conclusion, capillary proliferation occurs in the adult rat heart, and this process appears to be coupled with mast cell hyperplasia.

Animals↗

Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy.

Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HT through the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with p-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HT turnover.

Animals↗

Chronic total renal artery occlusion: a diagnostic challenge.

Chronic renal artery occlusion must be suspected whenever a moderate hypertensive patient over 50 years of age presents increase of blood pressure refractory to treatment, sometimes causing heart failure or stroke. This suspicion is reinforced by the presence of renal insufficiency and of anatomical and/or functional lateralization of renal damage at intravenous pyelography.

Adult↗

Asymmetry of neuronal activity during extracellular microelectrode recording from left and right human temporal lobe neocortex during rhyming and line-matching.

Recordings of neuronal activity in humans have identified few correlates of the known hemispheric asymmetries of functional lateralization. Here, we examine single-unit activity recorded from both hemispheres during two delayed match-to-sample tasks that show strong hemispheric lateralization based on lesion effects; a line-matching (LM) task related to the right hemisphere, and a rhyming (RHY) task related to the left. Nineteen neuronal populations were recorded with extracellular microelectrodes from the left temporal neocortex of 11 awake patients, and 18 from the right in 9 patients during anterior temporal lobectomy for complex partial seizures under local anesthesia. All subjects were left hemisphere dominant for language. Twelve (32%) populations exhibited statistically significant changes in activity at p <.05. Although changes in firing frequency were recorded from both hemispheres during both tasks, the RHY task elicited changes in activity several hundred milliseconds earlier on the left side than on the right. The LM task, on the other hand, induced changes earlier on the right side than on the left. Both hemispheres contained units active during verbal responses regardless of which behavior elicited the response. Our results indicate that cerebral dominance is reflected in earlier neuronal activity in the anterior temporal lobe during tasks lateralized to that hemisphere.

Adult↗

Effects of in vitro corticosteroids on B cell activation, proliferation, and differentiation.

The present study demonstrates the graded effect of in vitro corticosteroids (CSs) on the different phases of B cell activation, proliferation, and differentiation. Early events such as activation and proliferation of high-dose anti-mu or Staphylococcus aureus-stimulated B cells are profoundly suppressed by the presence of in vitro CSs. The suppressed proliferative response may be mediated by a direct effect on B cells and/or modulation of accessory cell function. Later events in the B cell cycle such as the proliferative response to B cell growth factor after either in vivo or in vitro activation are less sensitive to the suppressive effects of in vitro CSs. The final events in the B cell cycle; namely, the differentiation to the immunoglobulin-producing state, is not suppressed by in vitro CSs. Indeed, depending on the systems employed, there is either no effect or enhancement of immunoglobulin secretion by the presence of in vitro CSs. The graded effect of in vitro CSs on the discrete phases of the B cell activation, proliferation, and differentiation cycle provide new insights into the complex nature of CS-induced modulation of human B cell responses.

Adult↗

Non-significance of early speech delay in children with autism and normal intelligence and implications for DSM-IV Asperger's disorder.

According to the DSM-IV, children with Asperger's disorder do not have significant cognitive or speech delays, whereas children with autistic disorder may or may not. In our study, children with normal intelligence who had clinical diagnoses of autism or Asperger syndrome were divided into two groups: those with and without a significant speech delay. The purpose was to determine if clinically meaningful differences existed between the two groups that would support absence of speech delay as a DSM-IV criterion for Asperger's disorder. No significant differences were found between the 23 children with a speech delay and the 24 children without a speech delay on any of the 71 variables analyzed, including autistic symptoms and expressive language. Results suggest that early speech delay may be irrelevant to later functioning in children who have normal intelligence and clinical diagnoses of autism or Asperger syndrome and that speech delay as a DSM-IV distinction between Asperger's disorder and autism may not be justified.

Autistic Disorder↗

Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung.

Catecholamines trigger the switch from liquid secretion to absorption by perinatal lung, but regulation of Cl- and liquid secretion by pulmonary epithelia early in lung development (low [catecholamine]) is unknown. We looked for evidence for P1 and P2 receptors that mediate Cl- secretion in 14-d distal lungs and 14- and 18-d tracheas explanted from fetal rats (term = 22 d). We measured amiloride-insensitive transepithelial voltage changes induced by ATP, UTP, or adenosine. Explants were hyperpolarized by all three agonists and by terbutaline, a beta-adrenergic agonist and Cl- secretagogue. Whereas adenosine, ATP, or UTP injected into 14-d explant lumena, or adenosine added to the tracheal bath, induced hyperpolarization with EC50 of 2-15 microM EC50, values for all three agonists in the distal lung bath or ATP or UTP in the tracheal bath were five times greater. By 18 d, EC50 values for agonists in the bath were comparable to those for lumenal agonists (3-12 microM). In contrast, microinjection of terbutaline into all explant lumena (final concentration = 3 x 10(-5) M) induced minimal hyperpolarization, whereas the same concentration in the bath raised bioelectric potential difference maximally. We conclude that 1) beta-adrenergic receptors are present on the basolateral membranes of cells of the pulmonary epithelium early in lung development, and 2) adenosine, ATP, and UTP receptors are present in apical membranes throughout lung epithelial development, but basolateral receptors for these agonists in distal lung or ATP/UTP in trachea function later in gestation. The putative distribution of P1 and P2 receptors suggests a role for agonists released from pulmonary epithelial cells in the regulation of liquid secretion early in lung development.

Adenosine↗

Self-image among early adolescents: revisited.

Early adolescence is the developmental period during which children make the physical, psychological, cognitive, and social transitions to adolescence. Because the development of a healthy conceptualization of the self is foundational to adequate functioning later in life, self-image is a concept of interest to clinicians and researchers. Offer, Ostrov, and Howard (1981) conducted considerable research in the area and demonstrated that early adolescents have the capacity for self-reflection and are willing to share their reflections with others. Most early adolescents tend to be self-conscious due, chiefly, to the numerous physical and emotional changes occurring during this time period (M. P. Strommen & A. L. Strommen, 1985). Behavior is characterized by moodiness, impulsiveness, peer influence (Robin, 1985), and a growing resistance to authority. These factors usually result in an awkward child attempting to exert independence in an unprecedented fashion about a variety of topics (Manning, 1983). The purpose of this study was to investigate the self-image of early adolescents, aged 11 to 14 years, in order to plan for the health and developmental needs of middle school children and their families. Survey data were collected to answer the questions: (a) What is the self-image of a representative sample of middle school students in the community?; and (b) Are there differences in self-image based on gender, race, and parental occupation?

Adolescent↗

Simultaneous bilateral venous sampling for adrenocorticotropin in pituitary-dependent cushing's disease: evidence for lateralization of pituitary venous drainage.

At present it is not established whether lateralization of pituitary venous drainage occurs in humans. To explore this possibility, we performed bilateral simultaneous inferior petrosal sinus sampling for ACTH in three patients with surgically proven ACTH-secreting pituitary microadenomas laterally located in the pituitary gland. In each patient, a gradient for ACTH correctly identified the location of the tumor. This finding suggests that pituitary venous drainage in humans is lateralized. These data also demonstrate that inferior petrosal sinus sampling needs to be bilateral before the pituitary origin of ACTH hypersecretion can be safely excluded in patients with Cushing's syndrome. In at least one and possibly two patients, the pituitary origin of ACTH excess would have been missed had we only sampled one inferior petrosal sinus. Finally, the demonstration of a left to right central gradient for PRL in addition to ACTH in one patient suggests that this technique may be useful in lateralizing functioning pituitary tumors other than ACTH-secreting tumors.

Adenoma↗

Abnormalities of torsional fast phase eye movements in unilateral rostral midbrain disease.

In a patient with a unilateral rostral midbrain lesion, three-dimensional scleral search coil eye movement recordings demonstrated slowing of ipsidirectional torsional fast phase eye movements without any abnormalities of torsional slow phases. On high-resolution MRI, the brainstem lesion localized to the area of the efferent pathways from the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). This supports the experimental finding that unilateral inactivation of the riMLF results in a loss of ipsidirectional torsional fast phase eye movements and the hypothesis that there is lateralization of function throughout the torsional fast eye movement generating system.

Adult↗

Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats.

Although the optimal hematocrit during cardiopulmonary bypass (CPB) is not defined, excessive hemodilution may lead to organ ischemia via a reduction in oxygen-carrying capacity uncompensated by autoregulatory and/or rheologic increases in organ blood flow. As a result, the consequences of hemodilution in patients at risk for cerebral ischemia are not clearly understood. We designed this study to evaluate the effects of hemodilution in the setting of focal cerebral ischemia during CPB. Wistar rats surgically prepared for CPB were randomized to either hemodilution (hemoglobin (Hb), 6 g/dL; n = 9) or control (Hb, 11 g/dL; n = 8) groups and subsequently exposed to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Immediately after the onset of MCAO (maintained for 90 min), 65 min of hypothermic (28 degrees C) CPB was initiated. Twenty-four hours later, functional neurological outcome and cerebral infarct volume were determined. Compared with controls, the hemodilution group had worse neurological performance (new score = 8 [2], hemodilution; versus 10 [2], control; P = 0.030) and larger total cerebral infarct volumes (182 +/- 84 mm(3), hemodilution; versus 103 +/- 58 mm(3), control; P = 0.043). In this experimental model of CPB with reversible MCAO-induced focal cerebral ischemia, hemodilution worsened neurological function and increased cerebral infarct volume.

Animals↗