The root meristem is shaped by brassinosteroid control of cell geometry.

Growth extent and direction determine cell and whole-organ architecture. How they are spatio-temporally modulated to control size and shape is not well known. Here we tackled this question by studying the effect of brassinosteroid (BR) signalling on the structure of the root meristem. Quantification of the three-dimensional geometry of thousands of individual meristematic cells across different tissue types showed that the modulation of BR signalling yields distinct changes in growth rate and anisotropy, which affects the time that cells spend in the meristem and has a strong impact on the final root form. By contrast, the hormone effect on cell volume was minor, establishing cell volume as invariant to the effect of BR. Thus, BR has the highest effect on cell shape and growth anisotropy, regulating the overall longitudinal and radial growth of the meristem, while maintaining a coherent distribution of cell sizes. Moving from single-cell quantification to the whole organ, we developed a computational model of radial growth. The simulation demonstrates how differential BR-regulated growth between the inner and outer tissues shapes the meristem and thus explains the non-intuitive outcomes of tissue-specific perturbation of BR signalling. The combined experimental data and simulation suggest that the inner and outer tissues have distinct but coordinated roles in growth regulation.

Auxin requirements for a meristematic state in roots depend on a dual brassinosteroid function.

Root meristem organization is maintained by an interplay between hormone signaling pathways that both interpret and determine their accumulation and distribution. The interacting hormones Brassinosteroids (BR) and auxin control the number of meristematic cells in the Arabidopsis root. BR was reported both to promote auxin signaling input and to repress auxin signaling output. Whether these contradicting molecular outcomes co-occur and what their significance in meristem function is remain unclear. Here, we established a dual effect of BR on auxin, with BR simultaneously promoting auxin biosynthesis and repressing auxin transcriptional output, which is essential for meristem maintenance. Blocking BR-induced auxin synthesis resulted in rapid BR-mediated meristem loss. Conversely, plants with reduced BR levels were resistant to a critical loss of auxin biosynthesis, maintaining their meristem morphology. In agreement, injured root meristems, which rely solely on local auxin synthesis, regenerated when both auxin and BR synthesis were inhibited. Use of BIN2 as a tool to selectively inhibit BR signaling yielded meristems with distinct phenotypes depending on the perturbed tissue: meristem reminiscent either of BR-deficient mutants or of high BR exposure. This enabled mapping of the BR-auxin interaction that maintains the meristem to the outer epidermis and lateral root cap tissues and demonstrated the essentiality of BR signaling in these tissues for meristem response to BR. BR activity in internal tissues however, proved necessary to control BR levels. Together, we demonstrate a basis for inter-tissue coordination and how a critical ratio between these hormones determines the meristematic state.

Estimating wall guidance and attraction in mouse free locomotor behavior.

In this study, we estimate the influence exerted by the wall of the Open Field on the trajectory of the mouse. The wall exerts two types of influence on the mouse's path: one of guidance and one of attraction. The guiding influence is expressed by the tendency of mice to progress in parallel to the wall. This tendency wanes with increasing distance from the wall but is observed at large distances from it. The more parallel the mouse is to the wall the higher is its speed, even when distant from the wall. This association between heading direction and speed shows that the mouse controls its heading in reference to the wall. It is also observed in some blind strains, revealing that wall-guidance is not based exclusively on vision. The attraction influence is reflected by movement along the wall and by the asymmetry between speed during movement toward, and during movement away from the wall: sighted mice move faster toward the wall, whereas blind mice use similar speeds in both directions. Measures characterizing these influences are presented for five inbred strains, revealing heritable components that are replicable across laboratories. The revealed structure can lead to the identification of distinct groups of genes that mediate the distinct influences of guidance and attraction exerted by the wall. It can also serve as a framework for the decoding of electrophysiological data recorded in free moving rodents in the Open Field.

Lung perfusion scans in patients with congenital heart defects.

In 63 patients with various congenital heart defects, lung perfusion was evaluated with technetium-99mm macroaggregated albumin. Right lung perfusion abnormalities were documented in 34 patients (54%). A particularly high incidence occurred in patients who had undergone a systemic to pulmonary artery shunt operation as an initial palliative procedure or who had had right ventricular outflow reconstruction and in those with bilateral pulmonary artery stenosis. Serial studies were helpful in evaluating the functional results of different transcatheter interventions for optimizing pulmonary blood flow. The quantitative relative perfusion radionuclide method was a more sensitive means of detecting cases of abnormal lung perfusion than was chest radiology.

Molecular cloning and properties of the chicken leptin-receptor (CLEPR) gene.

The mammalian leptin receptor (LEPR) (formerly OB-R) mediates the weight regulatory effects of the circulating hormone leptin. The extreme obese phenotype of recessive mutations in the mouse leptin or LEPR genes (ob/ob and db/db mice, respectively) indicate the high potential of these genes for medical and agricultural research. In this paper, we report on the cloning of the full-length chicken leptin receptor (CLEPR) cDNA, which is the first non-mammalian cloning of a LEPR gene. The CLEPR gene shares a relatively low sequence similarity with its mammalian counterparts, with an average of 60% identical nucleotides. However, comparison between the predicted protein sequences has shown a tight conservation of most previously characterized LEPR motifs and essential tyrosine residues. Similarities between the chicken and the mammalian LEPR genes were also observed in the pattern of mRNA expression. The identification of the CLEPR gene should facilitate the study of the molecular mechanism involved in the regulation of body growth and composition in avian.

Albright hereditary osteodystrophy with hypothyroidism, normocalcemia, and normal Gs protein activity: a family presenting with congenital osteoma cutis.

The syndrome of Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP) and pseudopseudohypoparathyroidism (PPHP) is clinically and genetically heterogeneous. Classically, patients with PHP have the skeletal features of AHO, resistance to multiple hormones that work via cAMP such as parathyroid hormone and thyroid stimulating hormone, and deficient activity of Gs protein, the guanine nucleotide-binding protein that stimulates adenylate cyclase. However, patients without hormone resistance but with AHO and Gs deficiency were described (PPHP), as well as patients with multiple hormone resistance but without AHO or Gs deficiency. In a few patients with deficient Gs activity, hypothyroidism rather than hypocalcemia was the initial presentation of the disorder. We describe here a new variant of the syndrome, affecting 5 individuals in a 3 generation family with AHO, normal Gs activity and hypothyroidism. In the first 2 generations, mild features of AHO were present. The 2 sibs in the third generation had severe manifestations of AHO, including mild mental retardation as well as hypothyroidism. Diagnosis of congenital osteoma cutis at birth of the proband led to the diagnosis of the family. Elucidation of the molecular defect will shed light on the relationship between hormone resistance and AHO, as well as on the physiological mechanism of hormonal signal transduction.

Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).

OBJECTIVE: To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. DESIGN: Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. METHODS: Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. RESULTS: In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. CONCLUSIONS: The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium.

Bone age in adolescents with schizophrenia and obsessive-compulsive disorder.

The bone age (BA), height and weight of 20 adolescents with schizophrenia and 21 matched adolescents with obsessive-compulsive disorder (COD) were measured. The BA of the schizophrenic patients was significantly higher than their chronological age (CA)(p < 0.05), while the OCD subjects' BA was non-significantly lower than their CA. In addition, the difference between CA and BA (delta ages) in the schizophrenic adolescents was significantly different from the delta ages of the OCD adolescents (p , 0.05). Gender did not significantly affect BA or delta ages. A positive correlation (r = 0.5, p < 0.01) was obtained between CA and delta ages in the schizophrenic patients but not in the OCD patients. Both groups were within the normal range of weight and height percentiles.

Induction of thermotolerance in chickens by temperature conditioning: heat shock protein expression.

Broiler chicks were conditioned by exposure to heat stress early in life to elucidate physiological mechanisms and possible involvement of the known heat shock proteins (HSPs) in the induction of thermotolerance. Chicks were exposed to 36 +/- 1 degree C; 70-80% relative humidity (rh) for 24 hours at the age of 5 days. During conditioning, weight gain was depressed. Due to accelerated growth during the postconditioning period, a complete compensation for lost weight gain was achieved by the conditioned group. At the age of 42 days, challenge with acute heat stress of 35 +/- 1 degree C; 25-30% rh resulted in a large increase in cloacal temperature of the control chickens and by a more moderate increase in the conditioned chickens. Mortality during the thermal challenge was significantly higher in the control chickens than in the conditioned ones. Conditioning at an early age resulted in reduced plasma triiodothyronine (T3) concentration and hemodynamic changes (significant decrease in heart weight and hematocrit). The synthesis rate of 70 and 90 kDa HSPs during the first hour of heat challenge, accelerated gradually in control chickens, whereas in the conditioned chickens it accelerated only after 3 hours and in a more moderate response. These results suggest that HSP's response does not play a major role in the conditioning-induced mechanism leading to acquisition of thermotolerance in chickens.

Inflammatory pseudotumor in childhood. A diagnostic and therapeutic dilemma.

We describe a case of inflammatory pseudotumor of the lower abdomen in a young child. The urinary bladder and abdominal wall were involved, and the pseudotumor simulated a malignant sarcomatous tumor. Surgical excision was undertaken, and the outcome was favorable. This rare tumor simulates a true neoplasm both clinically and morphologically and presents a diagnostic and therapeutic dilemma. Our case and a review of the literature indicate that an effort should be made to perform a radical excision. This is considered the treatment of choice except if it requires a mutilating procedure.

MR findings in hereditary isolated growth hormone deficiency.

PURPOSE: To describe the MR characteristics by which patients with hereditary isolated growth hormone deficiency (GHD) can be distinguished from patients with other types of GHD. METHODS: A total of 51 patients with GHD were examined prospectively with MR imaging. On the basis of familial occurrence of GHD and genetic analysis, 10 patients met the criteria for hereditary deficiency. In each case, the height of the pituitary gland, the presence and location of the posterior neurohypophysis, and the completeness of the stalk were recorded. The findings in the hereditary group were compared with those in the rest of the patients. RESULTS: In all 10 patients with hereditary GHD, the adenohypophysis, the neurohypophysis, and the stalk were normal. Of the other 41 patients, the height of the gland was normal in three (7%), the neurohypophysis was abnormal in all, and the stalk was truncated in all but two patients (95%). CONCLUSIONS: The subgroup of patients with hereditary GHD exhibited an anatomically normal pituitary-hypothalamic region. This is in contrast to the majority of patients with idiopathic GHD. MR imaging can contribute to the classification of patients with GHD.

CT and MR evaluation of the brain in patients with anorexia nervosa.

Thirteen adolescent girls with anorexia nervosa had MR imaging of the brain; 11 were also examined by CT. Fifteen children, ages 10-12 years, served as a control group. The CT and MR studies were evaluated qualitatively for cortical and central atrophic changes. CT detected sulcal and ventricular enlargement in 5/11 patients. On the MR images, enlarged sulci were seen in 10/13 and dilated ventricles in 5/13. In the anorectic patients, the range of the width of the third ventricle was 1-5 mm (mean, 3.2 mm) and the maximal distance between the anterior horns was 22.5-39.0 mm (mean, 30.0 mm). Anterior horns at their minimal width measured 11-30 mm (mean, 16.5 mm). The corresponding measurements in the control group were 1.5-3.5 mm (mean, 2.3 mm) for the third ventricle, 21-35 mm (mean, 28.5 mm) for the distance between the anterior horns, and 10-16 mm (mean, 12.8 mm) for their minimal width. Overall, the patient group had larger ventricles than the control group; however, the difference between the two groups was not significant. Measurement of the number of visible cortical sulci at one cut below the vertex yielded 2-11 sulci in the anorectic girls (mean, 6.6) versus 0-6 sulci (mean, 3.3) in the controls. These results are statistically significant (p = .0009), indicating peripheral volume loss in the anorectic patients. The MR examination did not reveal any additional structural or parenchymal changes when compared with the results of the CT studies. However, the pituitary glands of these patients did not have the expected normal pubertal hypertrophy on the MR examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

MR findings in growth hormone deficiency: correlation with severity of hypopituitarism.

BACKGROUND AND PURPOSE: Growth hormone deficiency may present as an isolated deficit (IGHD) or in association with multiple deficiencies (MPHD). Previous studies have not compared the MR imaging findings with the severity of hypopituitarism. Our purpose was to determine whether MR imaging can distinguish between IGHD and MPHD. METHODS: Forty-four patients with growth hormone deficiency who were examined by MR imaging were included in this retrospective study. On the basis of the endocrinologic findings, 21 were determined to have IGHD and 23 to have MPHD. The presence, size, location, and morphologic characteristics of the stalk, the neurohypophysis, and the adenohypophysis were recorded in each case. Findings in the two groups were compared. Statistical significance was determined by t-test. RESULTS: The stalk was normal in one patient with IGHD and in none of those with MPHD; it was truncated or thin in 19 patients with IGHD (90%) and in only one with MPHD (4%); it was absent in 22 patients with MPHD (96%) and in only one patient with IGHD (5%). These differences between the two groups were highly significant. In 81% of the IGHD patients and in 91% of the MPHD patients the location of the neurohypophysis was ectopic. This difference between the two groups was not significant. Among IGHD patients, the adenohypophysis was of normal size in 13 patients (62%), small in six (29%), and absent in two (9%); the corresponding findings in MPHD patients were seven (30%), six (26%), and 10 (44%). CONCLUSION: The majority of IGHD patients had a truncated or thin stalk and a normal or small adenohypophysis. An absent stalk and adenohypophysis are characteristic of MPHD. MR imaging can contribute to the prediction of the pattern and severity of hypopituitarism in patients with growth hormone deficiency.

Optic pathway glioma: correlation of imaging findings with the presence of neurofibromatosis.

BACKGROUND AND PURPOSE: Despite the benign histology of optic pathway glioma (OPG) (low-grade astrocytoma), its biological behavior is unpredictable, and it is unclear whether specific morphologic or anatomic patterns may be predictive of prognosis. It is also unclear whether OPG associated with neurofibromatosis (NF) is a distinct entity from non-NF-OPG. Our purpose was to describe the MR imaging features of OPG, compare the findings between patients with and those without NF, and identify prognostic imaging signs. METHODS: MR examinations of 91 patients with OPG (47 with NF and 44 without) were reviewed at presentation and during follow-up. The images were evaluated for size and extension of tumor, and imaging parameters. Statistical bivariate analysis was used to compare the patients with and those without NF, and Pearson correlation was used to evaluate the correlation between the different imaging parameters and prognosis. Kappa values were calculated to determine intraobserver and interobserver variability. RESULTS: The most common site of involvement in the NF group was the orbital nerve (66%), followed by the chiasm (62%). In the non-NF group, the chiasm was the most common site of involvement (91%); the orbital nerves were involved in only 32%. Extension beyond the optic pathway at diagnosis was uncommon in the NF group (2%) but frequent in the non-NF group (68%). In the NF group, the tumor was smaller and the original shape of the optic pathways was preserved (91% vs. 27% in the non-NF group). The presence of cystic components was significantly more common in the non-NF patients (66% vs. 9% in the NF group). During follow-up, half the NF patients remained stable, in contrast to 5% of the non-NF group. No statistical correlation was found between imaging features and biological behavior of the tumor. CONCLUSION: NF-OPG is a separate entity from non-NF-OPG, with different imaging features and prognosis, thereby warranting a specific diagnostic, clinical, and therapeutic approach.

Disc space infection in children: magnetic resonance imaging.

The diagnosis of childhood intervertebral disc space infection is often delayed. Establishment of the correct diagnosis is imperative to preclude unnecessary procedures and to exclude other, more serious, diagnoses that would require aggressive management. MRI is a noninvasive technique that is very sensitive for disc space infection in children.

The natural history of osteonecrosis of the femoral head in children and adolescents who have Gaucher disease.

We reviewed the cases of eight patients (thirteen hips) with Gaucher disease who had had osteonecrosis of the femoral head and had been managed with bed rest and non-weight-bearing with crutches only in the symptomatic stage of the bone crisis. The mean age of the patients at the onset of the first crisis in each hip was ten years (range, six to fourteen years). The mean age at the most recent follow-up examination for the six living patients (ten hips) was twenty-three years (range, nineteen to thirty-three years). The Mose rating was good for one hip, fair for two, and poor for seven. Despite the over-all unfavorable radiographic ratings, the six patients were asymptomatic and did not need assistance with daily activities. There is no known treatment that effectively prevents the development of deformities of the femoral head. Thus, we recommend symptomatic management for osteonecrosis of the femoral head in Gaucher disease with bed rest and analgesics followed by non-weight-bearing on the involved limb, if it makes the patient more comfortable, during the symptomatic stage of bone crisis.

Bone scans in the diagnosis of bone crisis in patients who have Gaucher disease.

Of thirty-four occurrences of bone pain in seventeen children and young adults who had type-I Gaucher disease, twenty-five were finally diagnosed as bone crises. On the basis of a bone scan with technetium-99m methylene diphosphonate, a correct diagnosis of bone crisis was made for twenty-three occurrences, with a sensitivity of 0.92. At the onset of a crisis, the bone scan typically showed decreased uptake of radionuclide at the involved site. After six weeks, a repeat bone scan of the long bones showed a ring of increased uptake surrounding an area of decreased uptake. At six months, the appearance of the bones on the radionuclide scan was normal.

Preoperative localization of a foreign body by magnetic resonance imaging.

Nonradioopaque foreign bodies are very difficult to detect and localize. A case is presented in which a retained palm tree thorn was visualized and extracted with the help of magnetic resonance imaging.

Spinal involvement in children and adolescents with Gaucher disease.

Nineteen patients with type I Gaucher disease with spinal involvement first diagnosed during childhood, were followed for 2 to 24 years (average 9 years), and their clinical and radiologic history reviewed. Patients presented with three types of pain: mild pain that was defined as nonspecific, severe pain due to bone crisis, and pain associated with vertebral collapse. Collapse of vertebra occurred gradually anywhere along the thoraco-lumbar spine, and usually more than one vertebra was involved. In three patients, rectangular collapse was noted. Six patients suffered from central vertebra collapse, and two from anterior wedge compression. Further vertebral collapse with signs of root and cord compression developed in three patients as they grew. Awareness to the possibility of progressive vertebral collapse and periodic follow-up might prevent severe complications.