Experimental upper bound and theoretical expectations for parity-violating neutron spin rotation in 4He.

Neutron spin rotation is expected from quark-quark weak interactions in the standard model, which induce weak interactions among nucleons that violate parity. We present the results from an experiment searching for the effect of parity violation via the spin rotation of polarized neutrons in a liquid 4He medium. The value for the neutron spin rotation angle per unit length in 4He, d ϕ / d z = [ + 2.1 ± 8.3 (stat.) - 0.2 + 2.9 (sys.) ] × 10 - 7 rad/m, is consistent with zero. The result agrees with the best current theoretical estimates of the size of nucleon-nucleon weak amplitudes from other experiments and with the expectations from recent theoretical approaches to weak nucleon-nucleon interactions. In this paper we review the theoretical status of parity violation in the n → + 4He system and discuss details of the data analysis leading to the quoted result. Analysis tools are presented that quantify systematic uncertainties in this measurement and that are expected to be essential for future measurements.

A slow neutron polarimeter for the measurement of parity-odd neutron rotary power.

We present the design, description, calibration procedure, and an analysis of systematic effects for an apparatus designed to measure the rotation of the plane of polarization of a transversely polarized slow neutron beam as it passes through unpolarized matter. This device is the neutron optical equivalent of a crossed polarizer/analyzer pair familiar from light optics. This apparatus has been used to search for parity violation in the interaction of polarized slow neutrons in matter. Given the brightness of existing slow neutron sources, this apparatus is capable of measuring a neutron rotary power of dϕ/dz = 1 × 10(-7) rad/m.

Disease correction by combined neonatal intracranial AAV and systemic lentiviral gene therapy in Sanfilippo Syndrome type B mice.

Mucopolysaccharidosis type IIIB (MPS IIIB) or Sanfilippo Syndrome type B is a lysosomal storage disease resulting from the deficiency of N-acetyl glucosaminidase (NAGLU) activity. We previously showed that intracranial adeno-associated virus (AAV)-based gene therapy results in partial improvements of several aspects of the disease. In an attempt to further correct the disease, MPS IIIB mice were treated at 2-4 days of age with intracranial AAV2/5-NAGLU (IC-AAV), intravenous lentiviral-NAGLU (IV-LENTI) or the combination of both (BOTH). The BOTH group had the most complete biochemical and histological improvements of any treatment group. Compared with untreated MPS IIIB animals, all treatments resulted in significant improvements in motor function (rotarod) and hearing (auditory-evoked brainstem response). In addition, each treatment group had a significantly increased median life span compared with the untreated group (322 days). The combination arm had the greatest increase (612 days), followed by IC-AAV (463 days) and IV-LENTI (358 days). Finally, the BOTH group had nearly normal circadian rhythm measures with improvement in time to activity onset. In summary, targeting both the systemic and central nervous system disease of MPS IIIB early in life appears to be the most efficacious approach for this inherited metabolic disorder.

Direct nn-Scattering Measurement With the Pulsed Reactor YAGUAR.

Although crucial for resolving the issue of charge symmetry in the nuclear force, direct measurement of nn-scattering by colliding free neutrons has never been performed. At present the Russian pulsed reactor YAGUAR is the best neutron source for performing such a measurement. It has a through channel where the neutron moderator is installed. The neutrons are counted by a neutron detector located 12 m from the reactor. In preliminary experiments an instantaneous value of 1.1 × 10(18)/cm(2)s was obtained for the thermal neutron flux density. The experiment will be performed by the DIANNA Collaboration as International Science & Technology Center (ISTC) project No. 2286.

Biosynthesis of the linkage region of glycosaminoglycans: cloning and activity of galactosyltransferase II, the sixth member of the beta 1,3-galactosyltransferase family (beta 3GalT6).

A family of five beta1,3-galactosyltransferases has been characterized that catalyze the formation of Galbeta1,3GlcNAcbeta and Galbeta1,3GalNAcbeta linkages present in glycoproteins and glycolipids (beta3GalT1, -2, -3, -4, and -5). We now report a new member of the family (beta3GalT6), involved in glycosaminoglycan biosynthesis. The human and mouse genes were located on chromosomes 1p36.3 and 4E2, respectively, and homologs are found in Drosophila melanogaster and Caenorhabditis elegans. Unlike other members of the family, beta3GalT6 showed a broad mRNA expression pattern by Northern blot analysis. Although a high degree of homology across several subdomains exists among other members of the beta3-galactosyltransferase family, recombinant enzyme did not utilize glucosamine- or galactosamine-containing acceptors. Instead, the enzyme transferred galactose from UDP-galactose to acceptors containing a terminal beta-linked galactose residue. This product, Galbeta1,3Galbeta is found in the linkage region of heparan sulfate and chondroitin sulfate (GlcAbeta1,3Galbeta1,3Galbeta1,4Xylbeta-O-Ser), indicating that beta3GalT6 is the so-called galactosyltransferase II involved in glycosaminoglycan biosynthesis. Its identity was confirmed in vivo by siRNA-mediated inhibition of glycosaminoglycan synthesis in HeLa S3 cells. Its localization in the medial Golgi indicates that this is the major site for assembly of the linkage region.

Etiological point mutations in the hereditary multiple exostoses gene EXT1: a functional analysis of heparan sulfate polymerase activity.

Hereditary multiple exostoses (HME), a dominantly inherited genetic disorder characterized by multiple cartilaginous tumors, is caused by mutations in members of the EXT gene family, EXT1 or EXT2. The corresponding gene products, exostosin-1 (EXT1) and exostosin-2 (EXT2), are type II transmembrane glycoproteins which form a Golgi-localized heterooligomeric complex that catalyzes the polymerization of heparan sulfate (HS). Although the majority of the etiological mutations in EXT are splice-site, frameshift, or nonsense mutations that result in premature termination, 12 missense mutations have also been identified. Furthermore, two of the reported etiological missense mutations (G339D and R340C) have been previously shown to abrogate HS biosynthesis (McCormick et al. 1998). Here, a functional assay that detects HS expression on the cell surface of an EXT1-deficient cell line was used to test the remaining missense mutant exostosin proteins for their ability to rescue HS biosynthesis in vivo. Our results show that EXT1 mutants bearing six of these missense mutations (D164H, R280G/S, and R340S/H/L) are also defective in HS expression, but surprisingly, four (Q27K, N316S, A486V, and P496L) are phenotypically indistinguishable from wild-type EXT1. Three of these four "active" mutations affect amino acids that are not conserved among vertebrates and invertebrates, whereas all of the HS-biosynthesis null mutations affect only conserved amino acids. Further, substitution or deletion of each of these four residues does not abrogate HS biosynthesis. Taken together, these results indicate that several of the reported etiological mutant EXT forms retain the ability to synthesize and express HS on the cell surface. The corresponding missense mutations may therefore represent rare genetic polymorphisms in the EXT1 gene or may interfere with as yet undefined functions of EXT1 that are involved in HME pathogenesis.

Primary myxoma of the temporal bone in a 17-year-old boy: case report.

OBJECTIVE AND IMPORTANCE: Only two cases of primary intracranial myxomas have been described previously in the literature: one patient had a primary intracranial myxoma in the pituitary fossa, and the other patient's myxoma was located in the posterior fossa. CLINICAL PRESENTATION: A rare case of primary myxoma of the temporal bone in a 17-year-old boy is described. The patient presented with a history of progressive left-sided hearing loss and increasing headaches of a few months' duration. INTERVENTION: An initial draining procedure in the left ear revealed extant mucous material, and further investigation showed a large calcified lesion involving the petrous and temporal bones and filling the middle fossa. At surgery, a large mucoid-appearing tumor was removed. The tumor pathology revealed a primary myxoma with bone and meningeal involvement. No clinical or histopathological evidence that it was a metastatic lesion was found. CONCLUSION: The features of myxomas on computed tomographic and magnetic resonance imaging, the histopathology, and surgical considerations are discussed.

Cloning, Golgi localization, and enzyme activity of the full-length heparin/heparan sulfate-glucuronic acid C5-epimerase.

While studying the cellular localization and activity of enzymes involved in heparan sulfate biosynthesis, we discovered that the published sequence for the glucuronic acid C5-epimerase responsible for the interconversion of d-glucuronic acid and l-iduronic acid residues encodes a truncated protein. Genome analysis and 5'-rapid amplification of cDNA ends was used to clone the full-length cDNA from a mouse mastocytoma cell line. The extended cDNA encodes for an additional 174 amino acids at the amino terminus of the protein. The murine sequence is 95% identical to the human epimerase identified from genomic sequences and fits with the general size and structure of the gene from Drosophila melanogaster and Caenorhabditis elegans. Full-length epimerase is predicted to have a type II transmembrane topology with a 17-amino acid transmembrane domain and an 11-amino acid cytoplasmic tail. An assay with increased sensitivity was devised that detects enzyme activity in extracts prepared from cultured cells and in recombinant proteins. Unlike other enzymes involved in glycosaminoglycan biosynthesis, the addition of a c-myc tag or green fluorescent protein to the highly conserved COOH-terminal portion of the protein inhibits its activity. The amino-terminally truncated epimerase does not localize to any cellular compartment, whereas the full-length enzyme is in the Golgi, where heparan sulfate synthesis is thought to occur.

Solid and papillary epithelial neoplasm of the pancreas, diagnosis by cytology.

In this paper, I report a rare, low-grade malignant tumor, solid and papillary epithelial neoplasm of the pancreas (SPENP). I also discuss and review 157 previously reported cases. Unlike other malignant tumors of the pancreas, this neoplasm is typically found in young women, does not have metastases, and is amenable to cure after complete surgical resection. I discuss clinical features, diagnostic procedures, and differential diagnosis. Fine-needle aspiration can be effective in obtaining a preoperative diagnosis of SPENP, since the tumor has characteristic cytologic features. Also, use of clinical data, ultrasonography studies, computed tomography, magnetic resonance imaging, arteriography, and cytologic findings in the preoperative workup are important in obtaining an accurate diagnosis. Although potentially curable, late metastases and current inability to predict aggressive behavior by some tumors require lengthy follow-up.

Oral melanoacanthoma. Review of the literature and report of ten cases.

Melanoacanthoma is a simultaneous benign proliferation of two cell types--the keratinocyte and the melanocyte. It is a rare lesion; only twenty cases have been reported on skin and three cases intraorally. This article reports a series of ten cases of intraoral melanoacanthoma. Significant clinical differences exist between skin and mucosal lesions. Whereas the skin lesions occur almost exclusively in white persons and in an older population, the mucosal melanoacanthoma occurs in a much younger population, is seen almost exclusively among blacks, and is frequently associated with a history of trauma or irritation which precedes the rapid development of the lesion. Several cases have resolved with incomplete removal. It is conjectured that this lesion may represent a reactive phenomenon on oral mucosa rather than neoplasia.

Peripheral ameloblastoma. Report of a case.

The peripheral ameloblastoma is a rare tumor of the oral cavity, of which relatively few well-documented cases have been reported. A 54-year-old Caucasian male was found to have such a lesion in the posterior maxilla. The origin, histological appearance, and surgical treatment of this lesion is discussed. Histologically, the peripheral ameloblastoma is indistinguishable from the basal cell carcinoma, the occurrence of which is controversial in the oral cavity.

Small nonpolypoid carcinomas of the large intestine.

Two small carcinomas of the colon were examined, one an intramucosal carcinoma and the other a small carcinoma invading the submucosa. Serial sections did not reveal any adenomatous hyperplasia or polyps in the vicinity. The colonoscopist must be aware of the potential clinical importance of any small mucosal excrescence. Although several studies have indicated that most colonic carcinomas develop from an adenomatous polyp, some carcinomas apparently arise de novo. Further study of the epidemiologic, etiologic, and prognostic factors relating to these apparently uncommon lesions is indicated.

Gingival granula cell tumors of the newborn (congenital "epulis"): a clinical and pathologic study of 21 patients.

The clinical and pathologic features of 24 gingival granular cell tumors in newborns are reviewed. These tumors occurred exclusively in females and were localized on the anterior alveolar ridge (maxilla: 14; mandible: 9); the gingiva overlying future canine and lateral incisor teeth was most frequently involved. Follow-up data for 15 patients (average duration 15 years) indicated a lack of tumor recurrence despite incomplete resection in 11 instances. Tumors resected early in the newborn period were larger (maximum diameter 2.0 cm) and showed confluent to nodular submucosal growth with relatively less collagen. Some showed features suggesting involution. The histology in most cases supported a mesenchymal origin rather than one from odontogenic epithelium. Immunohistochemical staining for selected oncofetal and other antigens was negative. Electron microscopy did not entirely resolve the controversy regarding histogenesis.

Clinical evaluation of an algorithm for interpreting biochemical profiles showing hyperbilirubinemia.

An interpretive algorithm for biochemical profiles showing an elevated serum bilirubin concentration has been evaluated, modified, and retested in a retrospective clinical study, and is now being used at Charity Hospital in New Orleans to aid in the generation of interpretive comments to accompany the laboratory report. Further attempts to assess the clinical usefulness of this policy seem merited.

Granular cell tumor: a clinicopathologic study of 110 patients.

The clinicopathologic features of 118 granular cell tumors (GCT) encountered at two affiliated hospitals were reviewed. A total of 110 patients were affected over this 32-year period of study (71 men, 39 women), and in 5% GCT were multiple. Patients ranged in age from 16 to 58 years (average 32 years) and were symptomatic for an average duration of 11 months prior to diagnosis. There was a greater than expected frequency of GCT among black patients (29%). Although tongue was the single most common anatomic site involved, relatively more GCT (44%) occurred in skin or subcutaneous tissue. Less common locations were breast parenchyma (10 cases), rectal mucosa and anus (6), vulva (4), esophagus and larynx (2 cases each). The correct preoperative diagnosis of this protean tumor was made in only three patients. GCT were surgically treated with the average diameter of resected tumor being 1.2 cm (range 0.2--3.5 cm). Pseudoepitheliomatous hyperplasia was noted in 11 tumors and in one vulvar GCT there was overlying in situ squamous cell carcinoma. Tumors were incompletely excised in 24 of 56 patients having adequate followup; only five of these 24 patients experienced a local recurrence of tumor. Malignant behavior was not observed. Results of histochemical and ultrastructural study are briefly discussed. The precise histogenesis of GCT is uncertain but Schwann cell origin is favored in most cases.

Squamous-cell carcinoma arising in a lateral periodontal cyst.

A rare case of well-differentiated squamous-cell carcinoma arising in the epithelial lining of a lateral periodontal cyst is reported. Submission of surgically removed tissues for histopathologic evaluation is emphasized. The surgical site has been reconstructed and functions well. Because of early diagnosis and treatment, the patient has no evidence of clinical disease 2 1/2 years postoperatively.