Surface charge--induced ordering of the au(111) surface.

Synchrotron surface x-ray scattering (SXS) studies have been carried out at the Au(lll)/electrolyte interface to determine the influence of surface charge on the microscopic arrangement of gold surface atoms. At the electrochemical interface, the surface charge density can be continuously varied by controlling the applied potential. The top layer of gold atoms undergoes a reversible phase transition between the (1 x 1) bulk termination and a (23 x radical3) reconstructed phase on changing the electrode potential. In order to differentiate the respective roles of surface charge and adsorbates, studies were carried out in 0.1 M NaF, NaCl, and NaBr solutions. The phase transition occurs at an induced surface charge density of 0.07 +/- 0.02 electron per atom in all three solutions.

Two phases of Hox gene regulation during early Xenopus development.

We have shown previously that fibroblast growth factor (FGF) signalling in posterior regions of the Xenopus embryo is required for the development of the trunk and tail via a molecular pathway that includes the caudal-related gene Xcad3 and the posterior Hox genes [1]. These results have been contested by the work of Kroll and Amaya [2], which shows that Xenopus embryos transgenic for a dominant-negative form of the FGF receptor (FGF-RI) express posterior Hox genes normally, leading these authors to suggest that the FGFs are not required for anteroposterior (A-P) patterning of the dorsal axis. In order to investigate the apparent discrepancy between these studies, we have produced Xenopus embryos transgenic for two inhibitors of the FGF/Caudal pathway: a kinase-deficient dominant-negative FGF receptor (XFD) [3]; and a domain-swapped form of Xcad3 (Xcad-EnR) in which the activation domain of Xcad3 is replaced by the repression domain of the Drosophila Engrailed protein. Both of these were introduced as fusions with the green fluorescent protein (GFP), which allows identification of non-mosaic transgenic embryos at early gastrula stages by simply looking for GFP fluorescence. Analysis of gene expression in embryos transgenic for these constructs indicated that the activation of posterior Hox genes during early neurula stages absolutely requires FGF signalling and transcriptional activation by Xcad3, while the maintenance of Hox gene expression in the trunk and tail during later development is independent of both FGF and Xcad.

Molecular characterisation of a candidate gut sucrase in the pea aphid, Acyrthosiphon pisum.

The hydrolysis of sucrose, the principal dietary source of carbon for aphids, is catalysed by a gut alpha-glucosidase/transglucosidase activity. An alpha-glucosidase, referred to as APS1, was identified in both a gut-specific cDNA library and a sucrase-enriched membrane preparation from guts of the pea aphid Acyrthosiphon pisum by a combination of genomic and proteomic techniques. APS1 contains a predicted signal peptide, and has a predicted molecular mass of 68 kDa (unprocessed) or 66.4 kDa (mature protein). It has amino acid sequence similarity to alpha-glucosidases (EC 3.2.1.20) of glycoside hydrolase family 13 in other insects. The predicted APS1 protein contains two domains: an N-terminal catalytic domain, and a C-terminal hydrophobic domain. In situ localisation and RT-PCR studies revealed that APS1 mRNA was expressed in the gut distal to the stomach, the same localisation as sucrase activity. When expressed heterologously in Xenopus embryos, APS1 was membrane-bound and had sucrase activity. It is concluded that APS1 is a dominant, and possibly sole, protein mediating sucrase activity in the aphid gut.

Invasive properties of primary pediatric neoplasms in vitro.

Primary solid tumors were mechanically and/or enzymatically disassociated, and the resulting suspensions of single cells and small clumps of cells were seeded onto three different substrates, i.e., tissue culture plastic, rat smooth muscle cells (SMCs), and SMC-derived extracellular matrix. Tests of the relative effectiveness of these substrates in supporting the survival and/or growth of ten different neoplasms demonstrated that only two explants remained viable for longer than 2 weeks when seeded onto tissue culture plastic while nine of the ten survived on biological substrates for 1 month or longer. Thus, tissue culture plastic was a poor substrate for primary pediatric neoplasms. In general, more than 80% of the most common solid neoplasms in childhood (brain tumor, neuroblastoma, renal tumor, rhabdomyosarcoma, osteogenic sarcoma, and Ewing's sarcoma) routinely survived or grew in long-term cultures when cultured onto SMCs or their matrix. Both substrates were effective in promoting survival and/or growth; however, cells of neuroblastomas and certain brain tumors showed a preference for a living smooth muscle substrate. Tumor cells maintained their characteristic cellular and subcellular morphology when compared with the histology of the in vivo neoplastic lesions. Light and electron microscopy of selected neoplasms cultured on SMCs for various time periods demonstrated areas of distinct cellular invasion and/or partial destruction of the SMC multilayers which correlated with the invasive potentials of the neoplasms in patients. Invasion and destruction of the SMCs were also noticed with quiescent tumor cell cultures, indicating that growth was not a necessary property of invasion. Several neoplasms were also capable of the degradation of connective tissue proteins as indicated by the hydrolysis of radiolabeled SMC matrices, but simple correlations between the extent of matrix degradation and invasive ability could not be drawn. The culture system described consistently provided for the survival and/or growth of the most common pediatric tumors for long time periods. Thus, basic biological properties of primary tumors, e.g., growth, invasive potentials, and differentiation capabilities, could be investigated routinely.

Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.

Expression and functions of FGF-3 in Xenopus development.

We have analyzed the expression pattern of the Xenopus FGF-3 gene during early development and examined its biological activity in three different bioassays using Xenopus embryos. We show that from the early gastrula stage there is a domain of expression around the blastopore which becomes a posterior domain as the blastopore closes. An anterior ectodermal domain becomes detectable from mid-gastrula stages in the prospective hind-brain, and there are several later domains of expression: the midbrain-hindbrain junction, the otocyst, the pharyngeal pouches and the tailbud region. By using double whole-mount in situ hybridizations we show that the XFGF-3 expression in the brain is dynamically regulated both in time and space during development. The anterior domain of early neurula stage embryos corresponds to the prospective rhombomeres 3-5. By the time the neural tube is closed, XFGF-3 expression is restricted to r4 and later a new domain of expression is established at the midbrain/hindbrain junction. In addition, we show that, despite its difference in receptor specificity, XFGF-3 can induce the formation of mesoderm from animal caps similarly to other FGFs. It also displays a posteriorizing activity on whole embryos similar to other FGFs. Although the absence of maternal expression makes it unlikely that XFGF-3 is involved in mesoderm induction in vivo, its posterior domain of expression during gastrulation and its posteriorizing activity suggests that it participates in the maintenance of mesodermal gene expression and in the FGF mediated patterning of the anteroposterior axis during gastrulation.

eFGF is expressed in the dorsal midline of Xenopus laevis.

A detailed study of the expression pattern of embryonic fibroblast growth factor (eFGF) during early Xenopus development has been undertaken using whole-mount DIG in situ hybridization. We show that the zygotic expression of eFGF is activated in the mesoderm of the early gastrula and is first visualized as a ring around the blastopore, with significantly higher levels of expression on the dorsal side of the embryo. As gastrulation proceeds, eFGF transcripts become increasingly abundant in the dorsal blastopore lip. In the early neurula eFGF expression can be detected in the extreme posterior of the embryo around the closed blastopore and in the cells of the notochord. This latter result is significant and represents the first report of a Xenopus FGF that is expressed in the notochord. In addition, we show that during gastrula and neurula stages, expression of eFGF closely follows the expression of the Xenopus brachyury (Xbra) gene. During later development eFGF expression is localized to the tail-bud region and a stripe at the mid-brain/hind-brain junction. These data provide further evidence that FGFs play an important role in regulating the expression of brachyury in the developing mesoderm.

Myotonia dystrophica: Studies on gonadal function using luteinizing hormone-releasing hormone (LRH).

Eight men and four women with myotonia dystrophica were investigated. The gonadotropin responses to 100 mug luteinizing hormone-releasing hormone (LRH) were studied, and serum testosterone assayed. In the men with testicular atrophy a high basal follicle stimulating hormone was found with an exaggerated response to LRH. Although the mean basal luteinizing hormone was not significantly elevated, there was an excessive response to LRH, which was possibly conditioned by the lower mean testoerone levels in this group. This study provides biochemical indices of both the primary nature of the testicular damage and the disproportionately greater involvement of the seminiferous tubules. The pituitary-gonadal axis was normal in the women.

Clinical, endocrinological, and enzymatic characterization of two patients with 5 alpha-reductase deficiency: evidence that a single enzyme is responsible for the 5 alpha-reduction of cortisol and testosterone.

Two siblings with 46,XY male pseudohermapthroditism were demonstrated to have the phenotype characteristic of 5 alpha-reductase deficiency, namely normal testes and male Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle) terminating in a blind-ending vagina. Clitoromegaly was present at birth and increased further at the time of expected puberty. The diagnosis of 5 alpha-reductase deficiency was confirmed by demonstration of male levels of testosterone and testosterone precursors before and after hCG administration, elevated plasma testosterone to dihydrotestosterone and urinary etiocholanolone to androsterone ratios, and by in vitro studies indicating 5 alpha-reductase enzyme deficiency in the epididymis of one patient. Studies of control and mutant epididymal microsomes indicated that a single enzyme is responsible in the normal person for the 5 alpha-reduction of testosterone and cortisol (and probably other delta 4-3-ketosteroids as well) and that 5 alpha-reductase activity is undetectable for all substrates examined in the mutant. This finding explains why the formation of 5 alpha-reduced glucocorticoids is also defective in the disorder.

The role of fibroblast growth factors in early Xenopus development.

In recent years we and others have been attempting to identify the molecular nature of the inducing signals in early Xenopus development. We have found that most members of the fibroblast growth factor (FGF) family are biologically active as mesoderm-inducing factors when applied to ectoderm from blastulae. In addition to this, they will support continued expression of the pan-mesodermal transcription factor Xbra in the mesoderm of gastrula stage embryos. We have studied the expression pattern of four types of FGF in early embryos. Two types (FGF-2 and FGF-9) are expressed maternally and are thus present at the time of natural mesoderm induction. The expression of two other types (FGF-3 and FGF-4) is activated in the newly formed mesoderm of the gastrula. If the activity of the FGF family is inhibited by overexpression of a dominant-negative FGF receptor, there is a reduction in mesoderm formation, there are abnormalities arising from an inhibition of normal gastrulation movements and there is a defect in formation of the posterior parts. We believe that the mesoderm formation and cell movement effects are attributable to loss of Xbra expression, and the posterior defects to lack of posterior HOX gene activity. Overexpression of eFGF gives rise to a posteriorized phenotype, in which posterior HOX genes are expressed in a more anterior position. We conclude that the FGF system has multiple functions in early development, including mesoderm formation, gastrulation movements and anteroposterior patterning.

Metastatic medullary thyroid carcinoma in young children with mucosal neuroma syndrome.

Multiple endocrine neoplasia, type 2b (MEN 2b) is a disorder characterized by a distinct phenotype and a predisposition for medullary thyroid carcinoma (MTC) and pheochromocytoma. Two siblings aged 3 and 6 years with MEN 2b, who had elevated plasma calcitonin levels suggesting the presence of MTC are described. Microscopic foci of MTC were found in their thyroid glands and the glands were removed. In the younger child, a metastatic focus was present in a cervical lymph node. Of 12 previously reported children with MEN 2b and MTC who were less than 10 years of age at diagnosis, five had metastases. One of the present patients is the youngest described with this complication. The high frequency of metastases in very young patients with this syndrome has not been emphasized previously. These findings indicate the need for early diagnosis of MEN 2b and the importance of thyroidectomy at the earliest possible age when MTC is suspected by calcitonin screening tests.

Pseudorheumatoid nodule involving the orbit.

We report a clinicopathologic study of an unusual case of pseudorheumatoid nodule involving the right orbit of a child. Pathologically, the orbital lesion was similar to subcutanous nodules of rheumatoid arthritis and rheumatic fever. The physical findings and laboratory studies in our case did not reveal any evidence of systemic disease. Based on a review of reported cases involving other locations, this lesion appears clinically benign in children.

Autosomal recessive distal myopathy.

Five patients with an autosomally recessively transmitted distal myopathy were investigated. Of these, three belonged to a single sibship. Studies included electromyography, histological examination of muscle tissue, histochemical, electron microscopical, and biochemical analyses. One of the cases resembled the Nonaka form while the others were regarded as expressions of the commoner variety of recessive distal dystrophy.

Lipoblastoma and lipoblastomatosis--a report of six cases.

Lipoblastoma and lipoblastomatosis are rare examples of benign mesenchymal tumors that exhibit a tendency to invade locally but not to metastasize. The tumors are found primarily in children less than 5 years of age and can arise almost anywhere within the soft tissues. The rate of growth is variable and has no bearing on prognosis, which is excellent in the majority of cases. The experience at Childrens Hospital of Los Angeles with six children (3 males, 3 females) having these tumors is described. There was no instance of recurrence after surgical removal of the tumors, with follow-up periods ranging from 3 months to 5 years. Histologic appearance and outcome were similar in all patients, and there was no relationship between histologic appearance and prognosis. Complete local excision without radical mutilating resection is the treatment of choice.

Pulmonary sequestration in children: a twenty-five year experience.

Pulmonary sequestration occurs when some disturbance produces a cystic mass of nonfunctioning lung tissue which lacks normal communication with the tracheobronchial tree. In most cases the sequestered pulmonary tissue receives its blood supply from anomalous systemic vessels. This paper considers 15 children, 11 boys and four girls, ranging in age from one day to 14 years, with ten extralobar sequestrations and five intralobar pulmonary sequestrations. Although roentgenographic examination of the chest may suggest the diagnosis, conclusive diagnosis can only be obtained by arteriography and/or surgical exploration. Arteriography is strongly advocated in all cases, not only for its diagnostic value, but for its preoperative localization of the aberrant blood vessels that are the major technical concern to the surgeon.

Pyogenic granuloma presenting as a congenital epulis.

OBJECTIVE: To describe a clinical approach to the differential diagnosis of oral lesions in neonates. DESIGN: Case report. SETTING: Academic ambulatory care center. PARTICIPANTS: Male infant. RESULTS: A gingival mass in a male infant appeared clinically consistent with a congenital epulis. Following excision and histologic examination, the diagnosis was determined to be a pyogenic granuloma. Careful attention to alternative diagnoses led to the correct etiology. CONCLUSIONS: Primary care pediatricians encounter neonatal oral lesions infrequently. The most common oral lesions in the newborn period are Epstein pearls and Bohn nodules. This case illustrates the importance of formulating a more extensive differential diagnosis on discovery of a neonatal oral mass.

Mesenchymal hamartoma of the liver. A 35-year review.

Mesenchymal hamartoma of the liver occurs almost exclusively in infancy and childhood, with approximately 140 total cases reported. We report the experience with 18 patients at the Childrens Hospital of Los Angeles (Calif) during the past 35 years. The charts of all patients with mesenchymal hamartoma were retrospectively reviewed. The mean age at presentation was 16 months. Thirteen patients were symptomatic, presenting with increasing abdominal distention. Physical examination revealed an abdominal mass or hepatomegaly. Ultrasonography and computed tomography were the most useful diagnostic tests. Fourteen patients underwent resection; 9 underwent hepatic resection and 5 underwent excision of the tumor only. One patient had marsupialization, 1 underwent a biopsy only, and 2 died of unrelated causes and the hamartoma was found incidentally at autopsy. In all instances, a large cystic mass with well-demarcated margins was found. Three patients were unavailable for follow-up and 13 patients were alive and well 1 month to 24 years (mean, 5 years) after diagnosis. Recurrence or malignant transformation was not noted. A presumptive diagnosis can be made preoperatively by normal laboratory values and a combination of ultrasonography and computed tomography. We recommend excision of the tumor in all patients once the diagnosis is made, with the expectation of complete recovery.

Hamartomas of the chest wall in infants.

Chest wall hamartomas in infancy are rare lesions with distinct clinical, radiologic, and pathologic characteristics. Four cases treated at Children's Hospital of Los Angeles are presented and previously reported cases are reviewed. Chest wall hamartomas arise antenatally and present as hard, immobile masses, which may cause respiratory insufficiency. An extrapleural mass arising from the ribs can be seen radiographically. Histologically, these lesions are hypercellular and consist of a disorganized array of mesenchymal tissues endogenous to the chest wall. Rapid growth may occur, but usually is self-limited. Chest wall hamartomas are usually benign. This series includes the malignant transformation of one of these lesions. En bloc resection is curative, but the large residual chest wall defect frequently results in scoliosis.

Extraneural metastatic medulloblastoma during childhood.

From 1960 to 1977, 59 patients with histologically confirmed medulloblastoma were initially treated at Childrens Hospital of Los Angeles. Of this group, 49 have died and, of these, 34 were autopsied. Among the autopsied cases, 2 infants had neck masses that proved to be medulloblastoma that had spread from the cerebellar vermis before any surgical intervention. Four additional patients who had undergone a posterior fossa craniectomy without either the pre- or postoperative placement of a cerebrospinal fluid-diverting shunt were found to have extraneural metastatic medulloblastoma at autopsy. The extraneural metastatic medulloblastoma rate in the autopsied cases was 17.6% (6 of 34). Our series shows that the incidence of the extraneural spread of medulloblastoma is associated with being young, being male, and having diffuse tumor involvement of the subarachnoid space.

Benign and malignant ovarian tumors in children and adolescents. A review of 63 cases.

Sixty-three patients (15 months to 17 years of age) with ovarian tumors were seen. Fifty-six patients had germ cell tumors and 7 epithelial tumors, 6 patients had bilateral tumors, 47 patients had teratomas (41 benign, 3 with embryonic tissue, and 3 malignant), 6 germinomas, 1 endodermal sinus tumor, and 2 mixed germ cell tumors. Of the patients with epithelial tumors, six had cystadenomas and one cystadenocarcinoma. Abdominal pain was the most common symptom, and an abdominal mass the most common sign. A calcification on abdominal films was seen in 29 patients with benign teratoma. At surgery, the opposite ovary was bivalved or biopsied in 31 patients with benign tumors. Two patients had teratomas burried in the ovarian tissue. Among 47 patients with benign tumors, 37 have remained well after the operation and 10 were lost to follow-up. Two girls with embryonic teratoma are well 71 and 19 months after diagnosis but the third died with embryonal carcinoma. Of the 13 patients with malignant tumors, 8 are alive disease free 4 1/2 to 17 years after diagnosis, 4 are dead, and 1 is lost to follow-up (disease free 15 months after diagnosis).