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.

Abnormalities of the axial and proximal appendicular skeleton in adults with Laron syndrome (growth hormone insensitivity).

OBJECTIVE: To investigate abnormalities in the skeleton (with the exclusion of the skull, cervical spine, hands and feet) in patients with Laron syndrome, who have an inborn growth hormone resistance and congenital insulin-like growth factor-1 (IGF-1) deficiency. DESIGN AND PATIENTS: The study group was composed of 15 untreated patients with Laron syndrome (seven male and eight female) aged 21-68 years. Plain films of the axial and appendicular skeleton were evaluated retrospectively for abnormalities in structure and shape. The cortical width of the long bones was evaluated qualitatively and quantitatively (in the upper humerus and mid-femur), and the cortical index was calculated and compared with published references. Measurements were taken of the mid-anteroposterior and cranio-caudal diameters of the vertebral body and spinous process at L3, the interpedicular distance at L1 and L5, and the sacral slope. Thoracic and lumbar osteophytes were graded on a 5-point scale. Values were compared with a control group of 20 healthy persons matched for age. RESULTS: The skeleton appeared small in all patients. No signs of osteopenia were visible. The cortex of the long bones appeared thick in the upper limbs in 11 patients and in the lower limbs in four. Compared with the reference values, the cortical width was thicker than average in the humerus and thinner in the femur. The vertebral diameters at L3 and the interpedicular distances at L1 and L5 were significantly smaller in the patients than in the control subjects (P<0.001); however, at L5 the canal was wider, relative to the vertebral body. The study group had a higher rate of anterior osteophytes in the lumbar spine than the controls had, and their osteophytes were also significantly larger. In the six patients for whom radiographs of the upper extremity in its entirety were available on one film, the ulna appeared to be rotated. In one 22-year-old man, multiple epiphyses were still open. CONCLUSION: Congenital IGF-1 deficiency leads to skeletal abnormalities characterized by small bones, narrow spinal canal, and delayed bone age. The limitation in elbow distensibility common to patients with Laron syndrome may be related to a marked retroversion of the humeral head.

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.

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.

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.

Significance of residual abdominal masses in children with abdominal Burkitt's lymphoma.

PURPOSE: To evaluate the natural history of children with abdominal Burkitt's lymphoma who had complete clinical remission and residual abdominal mass after treatment. MATERIAL AND METHODS: The charts and imaging findings of all children with abdominal Burkitt's lymphoma treated and followed at our medical center between 1988 and 1999 were reviewed for the presence, management, clinical course, and prognosis of residual mass. RESULTS: Only children who achieved complete clinical remission were included. The study group consisted of 33 children (20 boys and 13 girls) aged 2.6-17.6 years (mean 7.2 years). Of these, seven (20.6 %) were found to have a residual abdominal mass. Two underwent second-look operation with no evidence of viable tumor on histology. The remaining five were followed by imaging studies for 2.2-9.1 years (mean 6.1 years); none relapsed. CONCLUSION: Residual mass is not uncommon in children with abdominal Burkitt's lymphoma. The presence of residual mass in a child with complete clinical remission does not alter the long-term prognosis. Therefore, in children with Burkitt's lymphoma and residual mass with no other signs of disease activity, expectant watching may be appropriate.

Intracranial cavernous hemangioma in a neonate.

Cogenital intracranial hemangioma is rare, and the imaging findings have been described in very few cases. We describe a case of a huge congenital left parietal hemangioma that was diagnosed postnatally by head duplex ultrasonography. Complete surgical resection yielded an excellent outcome.

Effect of P-glycoprotein expression on outcome in the Ewing family of tumors.

This study was designed to determine the prognostic significance of multidrug resistance, mediated by P-glycoprotein (Pgp) expression, in Ewing sarcoma. The clinical and laboratory features, treatment protocol, and outcome of 75 patients with Ewing sarcoma or peripheral neuroectodermal tumor treated between 1972 and 1997 were reviewed. Pgp expression was tested with the monoclonal antibody JSB-1. Thirty-four (64%) of the 53 tissue samples from untreated patients stained positive for Pgp. Progression-free and overall survival were 44 and 59%, respectively, in patients with negative findings, and 28 and 41% in those with positive findings; neither difference was significant. Of the 12 relapsed patients, 6 (50%) expressed more Pgp after chemotherapy than at diagnosis and 4 (33%) expressed less. Within these subgroups, 5 out of 6 and 3 out of 4 died from the disease. No correlation was found between Pgp and known prognostic factors of Ewing tumors. Pgp expression is probably an intrinsic factor of Ewing tumors but has no correlation to prognosis.

Acute diaphragmatic paralysis caused by chest-tube trauma to phrenic nerve.

A 3 1/2-year-old child developed unilateral diaphragmatic paralysis after chest drain insertion. Plain chest X-ray demonstrated paravertebral positioning of the chest-tube tip, and magnetic resonance imaging revealed hematomas in the region of the chest-tube tip and the phrenic nerve fibers. The trauma to the phrenic nerve was apparently secondary to malposition of the chest tube. This is a rare complication and has been reported mainly in neonates. Radiologists should notify the treating physicians that the correct position of a chest drain tip is at least 2 cm distant from the vertebrae.

New insight into calcinosis of juvenile dermatomyositis: a study of composition and treatment.

Milk of calcium developed in 2 children with juvenile dermatomyositis. The fluid of the collection contained macrophages, interleukin-6, IL-1, and tumor necrosis factor. The patient who had dystrophic calcinosis had a dramatic improvement with the introduction of alendronate. These findings suggest that calcinosis of juvenile dermatomyositis may be mediated by activated macrophages and that alendronate can be an effective treatment for this condition.

Tc-99m MIBI to evaluate children with Ewing's sarcoma.

PURPOSE: Tc-99m MIBI has been used increasingly to evaluate benign and malignant tumors because of its tumor-seeking properties and ability to provide an imaging assessment of multiple-drug resistance. This study investigated the clinical utility of Tc-99m MIBI in the management of Ewing's sarcoma in children. METHODS: Thirteen Tc-99m MIBI studies in nine (six male, three female) patients ages 6.5 to 20 years (mean, 13.4 years) with Ewing's sarcoma were reviewed. All patients had imaging studies at diagnosis, and four had follow-up studies during or after therapy. Scintigraphy was evaluated for Tc-99m MIBI uptake within the tumor and in metastases, which other imaging modalities had shown to be present in four patients. Scintigraphic results were correlated with the clinical course in all patients and with tumor P-glycoprotein status in six patients. RESULTS: Tc-99m MIBI accumulated in 6 of 9 primary tumors and did not accumulate in one recurrent tumor. No metastases showed Tc-99m MIBI uptake. The presence or absence of Tc-99m MIBI uptake at diagnosis or after therapy carried no prognostic significance. Tc-99m MIBI was present in the two tumors that were P-glycoprotein positive and in only one of four tumors that were P-glycoprotein negative. CONCLUSION: Tc-99m MIBI imaging does not appear to be useful in Ewing's sarcoma.

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.

Traumatic adrenal injury in children.

BACKGROUND: Multiple organ injury in children is an increasingly frequent phenomenon in the modern emergency room. Adrenal hemorrhage associated with this type of trauma has received little attention in the past. OBJECTIVES: Using computed tomography, we sought to determine the rate and nature of adrenal gland injury in children following blunt abdominal trauma due to motor vehicular accident. METHODS: A total of 121 children with blunt abdominal trauma were examined and total body CT was performed in cases of multi-organ trauma or severe neurological injury. RESULTS: Of all the children who presented with blunt abdominal trauma over a 51 month period, 6 (4.95%) had adrenal hemorrhage. In all cases only the right adrenal gland was affected. Coincidental injury to the chest and other abdominal organs was noted in 66.7% and 50% of patients, respectively. CONCLUSIONS: Traumatic adrenal injury in the pediatric population may be more common than previously suspected. Widespread application of the more sophisticated imaging modalities available today will improve the detection of damage to the smaller organs in major collision injuries and will help in directing attention to the mechanism of trauma.

Osteoid osteoma: resection with CT guidance.

BACKGROUND: Osteoid osteoma is a benign bone lesion characterized by nocturnal pain mostly, which may be relieved by non-steroidal prostaglandin inhibitors. Treatment by complete resection of the nidus immediately relieves the pain. Intraoperative location of the nidus may be difficult, and extensive bone resection may be necessary to ensure complete excision. Few studies have described resection of osteoid osteoma under CT guidance, and little attention has been given to lesions near the neurovascular bundle. OBJECTIVE: To report our results of osteoid osteoma resection under CT guidance, with specific attention to lesions lying near the neural structure. METHODS: Nine patients with suspected osteoid osteoma underwent resection with a 6.8 mm core drill under CT guidance. RESULTS: Histologic confirmation was obtained in seven patients, while in two there was no evidence of the nidus in the excised bone material. All nine reported complete pain relief immediately after the surgery. Postoperative CT scan showed complete removal of the osteoid osteoma. CONCLUSIONS: Removal of osteoid osteoma under CT guidance is simple, safe and allows complete removal of the nidus with low morbidity.

Visual pathway tumor: a heterogeneous tumor with a variable clinical course.

The aim of the study was to delineate the clinical characteristics of visual pathway tumor in children without neurofibromatosis-I. The authors reviewed the charts of all patients meeting these criteria (n = 12) who were followed in their center over a 13-year period. In 8 patients the disease was relentlessly progressive, and imaging showed a chiasmatic/hypothalamic, exophytic globular lesion. The remainder had a benign course with long periods of tumor stability; one showed some spontaneous visual improvement. The lesions of the latter subgroup were multilobular, with elongated posterior extension into the optic tract. This differentiation, according to the imaging findings, may have significant therapeutic implications. In the first type, every effort should be made to arrest the disease and decrease the size of the lesion, whereas in the second, despite decreased visual ability, careful observation in the appropriate approach. There are as yet no known biological markers to better delineate these two types of tumor behavior.

The chicken leptin gene: has it been cloned?

The DNA sequence of a chicken leptin gene that shares 95% nucleotide similarity with the mouse leptin sequence has been recently reported (Taouis et al., 1998, Gene 208, 239-242). Experiments have been performed independently in two laboratories to try to confirm this finding. Fourteen PCR primers based on the mouse leptin sequence were designed to amplify the avian leptin gene. Four of the primers were identical to the mouse and published chicken leptin sequences. PCR amplification was carried out on genomic DNA and reverse-transcribed mRNA from the fat, liver, and pancreas of several chicken strains and from the domestic turkey, goose, and Japanese quail. No PCR products sharing close similarity to the mouse leptin sequence were generated from any avian templates. Amplification of mouse leptin sequence was consistently obtained when control mouse templates were used. Northern hybridization using a mouse leptin probe failed to produce a signal with poly(A)+ RNA from chicken fat and liver and from the fat and liver of force-fed geese but a strong signal was obtained from control mouse fat total RNA. Southern hybridization under low stringency washing conditions revealed hybridization of a mouse leptin probe to chicken genomic DNA. Under higher stringency washing conditions, the chicken signal disappeared, while those from control mouse and sheep genomic DNA remained. This suggests that the putative chicken leptin sequence shares less than the 83% nucleotide sequence identity between the mouse and sheep genes. It is concluded that a chicken leptin gene sequence with close sequence similarity to mouse leptin is not present in the chicken genome. Furthermore, mRNA sharing high sequence identity with mouse leptin is not present in the fat or liver of the domestic chicken, turkey, goose, or Japanese quail.

Prevalence and new phenotypic and radiologic findings in congenital onychodysplasia of the index finger.

Congenital onychodysplasia of the index finger (COIF) is a rare condition characterized by dysplastic changes in the nail with variable phenotypic manifestations. Its prevalence is unknown. We describe three newborn patients with various clinical and radiologic expressions of this entity. The first, born to a mother treated with multiple antidepressant drugs, had bilateral nail dysplasia of the index finger without bony involvement. The second presented with bilateral hypoplastic nail of the index finger and bilateral symphalangism of the fifth finger; aplastic distal phalanges of the second finger was also noted radiologically. The third baby (born to a diabetic mother treated with insulin), had micronychia and brachydactyly of the right index finger and syndactyly of the second and third fingers; the radiologic finding was bilateral brachymesophalangia of the index finger. It would seem that, besides the nail dysplasia of the index finger, COIF may also be associated with bone dysplasia of the same finger.

Involvement of the foot and ankle in patients with Gaucher disease.

Of 48 children with type I Gaucher disease treated at our hospital, 11 had involvement of the foot and ankle that first appeared in adolescence. Follow-up ranged from 3 to 27 years (average, 10 years). We reviewed their clinical and radiographic histories. Patients presented with four types of pain: six (7 events of pain) complained of dull pain defined as nonspecific; seven (11 events) had severe pain caused by bone crisis; two (2 events) had moderate progressive pain caused by pathological fractures; and one had painful swollen ankles caused by degenerative arthritis. Greater awareness of these complications in patients with Gaucher disease will prevent misdiagnosis and lead to early treatment.