The traumatic anterior overbite

The position of the anterior teeth and skeletal base relationship establish many of our facial characteristics, yet these same tooth positions can result in a range of dental problems that are often specific for a particular incisal relationship. Excessive loss of tooth tissue on various surfaces may result in trauma to the soft tissue and temporomandibular joint dysfunction. A range of treatment options may be required and can often be conveniently classified by the form of incisal relationship.     

Distribution of monoclonal antibodies in intestinal and urogenital secretions of mice bearing hybridoma ''backpack'' tumours

Primary Epstein-Barr virus (EBV) infection may manifest itself as a benign lymphoproliferative disorder, infections mononucleosis (IM). EBV infection has been characterized in lymphoreticular tissues from nine patients with IM using the abundantly expressed EBV-encoded nuclear RNAs (EBERs) as a marker of latent infection. Expression of the virus-encoded nuclear antigen (EBNA) 2 and of the latent membrane protein (LMP) 1 was seen in variable proportions of cells in all cases. Double labelling revealed heterogeneous expression patterns of these proteins. Thus, in addition to cells revealing phenotypes consistent with latencies I (EBNA2-/LMP1-) and III (EBNA2+/LMP1+), cells displaying a latency II pattern (EBNA2-/LMP1+) were observed. Cells expressing EBNA2 but not LMP1 were also detected; whilst this may represent a transitory phenomenon, the exact significance of this observation is at present uncertain. EBER-specific in situ hybridization in conjunction with immunohistochemistry revealed expression of the EBERs mainly in B-lymphocytes, many of which showed features of plasma cell differentiation. By contrast, convincing evidence of latent EBV infection was not found in T-cells, epithelial or endothelial cells. Double-labelling immunohistochemistry revealed expression of the replication-associated BZLF1 protein in small lymphoid cells, often showing plasmacytoid differentiation. There was no unambiguous expression of this protein in other cell types. These results suggest that B-cells are the primary target of EBV infection and that plasma cells may be a source of infectious virus found in the saliva of IM patients.     

Mapping the structural domains of E. coli carbamoyl phosphate synthetase using limited proteolysis

The structural and functional domains of Escherichia coli carbamoyl phosphate synthetase (CPS) have been identified by limited proteolysis. Incubation of CPS with several proteases, including trypsin, chymotrypsin, subtilisin and endoproteinase Asp-N, under native conditions, causes a time-dependent loss of enzymatic activity and the generation of a common fragmentation pattern. Amino-terminal sequencing studies demonstrated that the initial cleavage event by trypsin occurred at the carboxy-terminal end of the large subunit. The ultimate fragments produced in most of the proteolysis studies, 35- and 45-kDa peptides, were derived from areas corresponding to the putative ATP binding regions. Substrate protection studies showed that the addition of ligands did not affect the final fragmentation pattern of the protein. However, ornithine and UMP were found to significantly reduce the rate of inactivation by inhibition of proteolytic cleavage. MgATP and IMP provided modest protection whereas bicarbonate and glutamine showed no overall effect on proteolysis. Limited proteolysis by endoproteinase Asp-N resulted in the production of a fragment (or multiple fragments) which contained enzymatic activity but had lost all regulation by the allosteric ligands, UMP and ornithine. The small subunit has been shown to be protected from proteolysis by the large subunit. Proteolysis of the isolated small subunit resulted in the generation of a stable 31-kDa species which contained 10% of the original glutaminase activity. These studies demonstrate that a portion of the C-terminal end of the large subunit can be excised without entirely destroying the ability of CPS to catalyze the formation of carbamoyl phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microcephaly with chorioretinopathy. A report of two dominant families and three sporadic cases

This study was designed to assess the effect of paraquat on the rat kidney. The experimental animals used were Wistar rats, a strain selected and maintained at the Institut d'hygiène alimentaire. Their diet was well defined and their state of health monitored. Female animals with mean weight of 200 g were used in this study. Doses of 20, 30 and 50 mg/kg were administered via the gastrointestinal route. In this experimentation, performed on 12 rats plus 3 controls, the dose considered to be sublethal was 30 mg/kg administered by gavage. These animals were sacrificed after 24 h, 48 h, 4, 8, 15, 30 and 60 day, selecting those animals with the most severely altered state, at each time. Tubular lesions started to appear by the 24th hour; the proximal tubule was the most sensitive. Lesions of the distal tubule were observed slightly later, from the 48th hour. Lesions became more intense from the 4th day onwards and reached a maximum on the 8th day. The first signs of repair of the proximal tubule and distal tubule were observed on the 15th day, but were less marked for the proximal tubule. This repair was slow and progressive. Persistent lesions of the proximal or distal tubules were still observed after two months. The glomeruli presented several alterations, which were always only moderate. Overall, paraquat induces serious life-threatening lesions of acute tubular necrosis in the absence of adequate intensive care.     

A pilot study of gamma-1b-interferon in combination with fluorouracil, leucovorin, and alpha-2a-interferon

The combination of IFN-alpha-2a (IFN-alpha) and IFN-gamma-1b (IFN-gamma) has been found to produce more than additive cytotoxicity with fluorouracil (5-FU) in HT 29 colon cancer cells due to enhanced DNA-directed effects. We therefore studied the combination of IFN-gamma with IFN-alpha, 5-FU, and leucovorin (LV) in a clinical trial. Fifty-three patients received an initial cycle of 5 million units (MU)/m2 IFN-alpha s.c. on days 1-7 with 500 mg/m2 LV and 370 mg/m2 5-FU i.v. on days 2-6. IFN-gamma was then added once tolerable doses of 5-FU and IFN-alpha were established for each patient. IFN-gamma was administered at one of six dose levels between 0.3-4.8 MU/m2 s.c. on days 1-7. This design permitted comparison of the clinical toxicity and pharmacokinetics of 5-FU in two consecutive cycles in an individual treated with the same doses of 5-FU/LV/IFN-alpha in the absence and presence of IFN-gamma. In 43 matched patient cycles, the addition of IFN-gamma did not seem to worsen gastrointestinal toxicity, and skin toxicity tended to be milder. 5-FU clearance was higher in 14 cycles with IFN-gamma compared to the patient's prior cycle with the same doses of 5-FU/LV/IFN-alpha: 798 +/- 309 versus 601 +/- 250 ml/min/m2 (mean +/- SD; P = 0.04). In these 28 cycles, the median 5-FU clearance was significantly lower in 11 cycles that were complicated by more severe diarrhea: 524 versus 798 ml/min/m2 (grade 2 versus 0-1; P = 0. 0032). Overall, 38% and 26% of patients had grade 3-4 diarrhea and mucositis. Dose reductions of IFN-gamma for chronic fatigue, malaise, or anorexia were ultimately required more frequently with >/=2.4 MU/m2 (P = 0.018), and the maximum tolerated dose of IFN-gamma was considered to be 1.2 MU/m2/ day. Objective responses were seen in 41% of 29 measurable colorectal cancer patients. Compared to our previous experience with 5-FU/LV/IFN-alpha, IFN-gamma and IFN-alpha appeared to have opposite effects on 5-FU clearance. These results suggest that any potential benefit of adding IFN-alpha to 5-FU/LV on this schedule may not depend solely on alterations in 5-FU clearance.     

Pulp reactions to restoration of experimentally induced crown fractures

OBJECTIVES: Reattachment of the avulsed enamel-dentine coronal fragment to the remaining tooth structure has become an accepted clinical alternative to a resin composite build-up for the restoration of crown fractured teeth. Since little knowledge exists as to the pulpal response to this procedure, this study was designed to observe the condition of the pulp following experimentally induced crown fracture and restoration in monkeys. METHODS: Experiments were conducted in eight young green Vervet monkeys (Cercopithecus aethiops). In all, 64 fractured incisors were investigated. Light microscopic examination of pulp tissue specimens was carried out after 3 months of observation. RESULTS: The evaluation was restricted to specimens having a fracture plane within 2 mm of the pulp and no pulpal exposure. In general, pulp tissue was well preserved irrespective of the restorative procedure. Even if the restoration or the bonded tooth fragment had been lost during the follow-up period, the pulp generally remained in good condition. Inflammatory infiltrates where seen in only a few specimens and then as clusters of mononuclear leukocytes. Hard tissue repair was frequently observed and displayed various configurations from isolated hard tissue deposits to areas of extensive hard tissue repair in the coronal portion of the pulp. Pronounced hard tissue repair and occurrence of inflammatory cell infiltrates correlated with the presence of stainable bacteria on the fractured dentine surface. CONCLUSIONS: In the absence of direct exposure, reparative dentine is a frequent feature of the pulp's response to crown fracture and restoration with composite or reattachment of the crown fragment with dentine bonding. These restorative procedures appear to ensure continued function of the underlying pulp.     

Analysis of the roles of antilipopolysaccharide and anti-cholera toxin immunoglobulin A (IgA) antibodies in protection against Vibrio cholerae and cholera toxin by use of monoclonal IgA antibodies in vivo

Secretory immunoglobulin A (IgA) antibodies (sIgA) directed against cholera toxin (CT) and surface components of Vibrio cholerae are associated with protection against cholera, but the relative importance of specific sIgAs in protection is unknown. A monoclonal IgA directed against the V. cholerae lipopolysaccharide (LPS), secreted into the intestines of neonatal mice bearing hybridoma tumors, was previously shown to provide protection against a lethal oral dose of 10(7) V. cholerae cells. We show here that a single oral dose of 5 to 50 micrograms of the monoclonal anti-LPS IgA, given within 2 h before V. cholerae challenge, protected neonatal mice against challenge. In contrast, an oral dose of 80 micrograms of monoclonal IgA directed against CT B subunit (CTB) failed to protect against V. cholerae challenge. A total of 80 micrograms of monoclonal anti-CTB IgA given orally protected neonatal mice from a lethal (5-micrograms) oral dose of CT. Secretion of the same anti-CTB IgA antibodies into the intestines of mice bearing IgA hybridoma backpack tumors, however, failed to protect against lethal oral doses of either CT (5 micrograms) or V. cholerae (10(7) cells). Furthermore, monoclonal anti-CTB IgA, either delivered orally or secreted onto mucosal surfaces in mice bearing hybridoma tumors, did not significantly enhance protection over that provided by oral anti-LPS IgA alone. These results demonstrate that anti-LPS sIgA is much more effective than anti-CT IgA in prevention of V. cholerae-induced diarrheal disease.