DNA sequence and comparative analysis of chimpanzee chromosome 22.

Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.

Molecular cloning and characterization of a gene expressed in mouse developing tongue, mDscr5 gene, a homolog of human DSCR5 (Down syndrome Critical Region gene 5).

For understanding the pathogenesis of Down syndrome (DS), it is important to identify and characterize the genes on Chromosome (Chr) 21, especially those in the Down syndrome critical region (DSCR) on Chr 21q22.2. Recently we have determined 33.5 Mb (more than 99%) of DNA sequence of Chr 21 and, from these sequence data, we identified a novel gene, DSCR5 (transcript = 0.8 kb), from DSCR by combination of computational gene prediction and cDNA screening. For functional analysis of DSCR5, we identified a mouse homolog of the DSCR5 cDNA, and termed it mDscr5 (transcript length = 0.8 kb). The gene was mapped to mouse Chr 16 C3-C4, the syntenic region of human Chr 21, and encodes an amino acid of 132 residues with 90% identity to DSCR5. In situ hybridization showed that mDscr5 is predominantly expressed in the developing tongue. To our best knowledge, no other gene in DSCR is reported to be expressed in tongue, so that DSCR5 may be the first candidate to elucidate the pathophysiology of tongue malformation observed in DS.

Architecture and anatomy of the genomic locus encoding the human leukemia-associated transcription factor RUNX1/AML1.

The RUNX1 gene on human chromosome 21q22.12 belongs to the 'runt domain' gene family of transcription factors (also known as AML/CBFA/PEBP2alpha). RUNX1 is a key regulator of hematopoiesis and a frequent target of leukemia associated chromosomal translocations. Here we present a detailed analysis of the RUNX1 locus based on its complete genomic sequence. RUNX1 spans 260 kb and its expression is regulated through two distinct promoter regions, that are 160 kb apart. A very large CpG island complex marks the proximal promoter (promoter-2), and an additional CpG island is located at the 3' end of the gene. Hitherto, 12 different alternatively spliced RUNX1 cDNAs have been identified. Genomic sequence analysis of intron/exon boundaries of these cDNAs has shown that all consist of properly spliced authentic coding regions. This indicates that the large repertoire of RUNX1 proteins, ranging in size between 20-52 kDa, are generated through usage of alternatively spliced exons some of which contain in frame stop codons. The gene's introns are largely depleted of repetitive sequences, especially of the LINE1 family. The RUNX1 locus marks the transition from a ~1 Mb of gene-poor region containing only pseudogenes, to a gene-rich region containing several functional genes. A search for RUNX1 sequences that may be involved in the high frequency of chromosomal translocations revealed that a 555 bp long segment originating in chromosome 11 FLI1 gene was transposed into RUNX1 intron 4.1. This intron harbors the t(8;21) and t(3;21) chromosomal breakpoints involved in acute myeloid leukemia. Interestingly, the FLI1 homologous sequence contains a breakpoint of the t(11;22) translocation associated with Ewing's tumors, and may have a similar function in RUNX1.

Teaching an abbreviated impression technique for complete dentures in an undergraduate dental curriculum.

STATEMENT OF PROBLEM: Traditional methods for teaching complete denture fabrication are time-consuming, difficult to master, and not used by many general practitioners. PURPOSE: This study compared the efficacy of traditional denture fabrication techniques with a more abbreviated method in a dental school setting. MATERIAL AND METHODS: A retrospective record review of 80 completely edentulous patients treated by predoctoral dental students was completed. Forty patients were treated with traditional denture techniques; the other 40 patients were treated with an abbreviated method. The data abstracted included the number of visits to completion and the number of postinsertion visits and relines required within the first 3 months after delivery. A Wilcoxon rank sum test was performed to determine statistical significance between the groups with regard to number of visits for fabrication and postinsertion adjustments. A test for a difference in proportions by using the normal approximation to the binomial distribution was performed for statistical analysis of the incidence of relines. RESULTS: The abbreviated denture technique resulted in a statistically significant difference in the number of visits for fabrication (P<.01) and postinsertion adjustments (P<.05.) There was no difference (P=.39) in the number of relines between the 2 groups. CONCLUSION: Teaching the abbreviated complete denture technique in an undergraduate dental clinic decreased the number of appointments necessary to complete denture therapy without increasing the number of adjustments or reline procedures.

Retentiveness of dental cements used with metallic implant components.

There is limited dental literature evaluating the retentive capabilities of luting agents when used between metal components, such as cast metal restorations cemented onto machined metal implant abutments. This study compared the retentive strengths of 5 different classes of luting agents used to cement cast noble metal alloy crowns to 8-degree machined titanium cementable implant abutments from the Straumann ITI Implant System. Sixty prefabricated 5.5-mm solid titanium implant abutments and implants were used; 30 received the standard surface preparation and the other 30 received an anodized surface preparation. Anodized implant components were used to reflect current implant marketing. Sixty castings were fabricated and randomly paired with an abutment and implant. A total of 12 castings were cemented onto the implant-abutment assemblies for each of the 5 different luting agents (zinc phosphate, resin composite, glass ionomer, resin-reinforced glass ionomer, and zinc oxide-non-eugenol). After cementation, the assemblies were stored in a humidor at room temperature prior to thermocycling for 24 hours. Each casting was pulled from its respective abutment, and the force at which bond failure occurred was recorded as retentive strength. A statistically significant difference was found between the 5 cements at P < or = .001. Of the cements used, resin composite demonstrated the highest mean retentive strength. Zinc phosphate and resin-reinforced glass-ionomer cements were the next most retentive, while glass ionomer and zinc oxide-non-eugenol cements demonstrated minimal retention. In addition, retention was not altered by the use of an anodized abutment surface.

A novel gene, DSCR5, from the distal Down syndrome critical region on chromosome 21q22.2.

Based on a detailed sequence of the distal Down syndrome critical region (DSCR), we predicted and molecularly cloned a novel gene, designated DSCR5. We determined the sequences of expressed sequence tags (ESTs) that almost matched the predicted cDNA sequence of DSCR5. Northern blot analysis showed that DSCR5 is expressed in several tissues including the liver, skeletal muscle, heart, pancreas and testis. To determine the 5'-end of DSCR5, the oligo-capping method was employed. Combining the EST sequence data and that from the oligo-capping experiments, we obtained the full-length cDNA sequence of DSCR5. DSCR5 had at least four types of alternatively spliced variants. According to the number of exons, they could be classified into two subtypes: DSCR5alpha and DSCR5beta. DSCR5alpha includes three splice variant subtypes, DSCR5alpha1, alpha2 and alpha3, which each has different first non-coding exon. In addition, the most abundantly isolated form, DSCR5alpha1, shows microheterogeneity of the mRNA start site. Comparison of the sequences between the predicted cDNA and the molecularly cloned cDNA revealed that the computer programs had limited validity to correctly predict the terminal exons. Thus, molecular cloning should always be required to complement the inadequacy of the computer predictions.

The DNA sequence of human chromosome 21.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Prosthodontic considerations.

The prosthodontic section of the 1997 ITI Consensus Conference in Vitznau, Switzerland, examined a broad spectrum of issues related to the prosthodontic phase of dental implant therapy. Topics included diagnosis and treatment planning, considerations for the use of ITI prosthodontic components, management of the partially edentulous patient, management of the edentulous patient, implant occlusion, and the use of narrow- and wide-body implants. The management of partially and totally edentulous patients will be discussed in separate papers. This paper is written so that each major consensus point discussed by the prosthodontic section is the first sentence of a paragraph. The remainder of each paragraph serves as background information or justification for the consensus statement. It should be noted that agreement on all points was reached by voting within the prosthodontic section. Many of the consensus statements were reached unanimously, while some were reached through compromise and split vote. Not all of the points presented here were presented to the plenum session on the final day of the conference.

Management of the edentulous patient.

Being edentulous is a handicap, and the main objective of implant placement is to provide support of fixed prostheses or to stabilize complete dentures in the edentulous jaw. Clinical experience and clinical studies have demonstrated the broad application of non-submerged ITI implants in prosthetic therapy in standard sites and in situations of advanced atrophy or substantial loss of tissue. The ITI implant was developed for universal use in partially and completely edentulous patients and for replacement of single missing teeth. The abutment system offers the choice of both removable and fixed prostheses with identical secondary parts. The present article describes the use of ITI implants for prosthodontic rehabilitation in the completely edentulous jaw. Indications and various types of fixed or removable prostheses, alternatives and variations of design are discussed. Prosthetic design is dependent on the number and location of implants, and conversely, the number of implants that can be placed will determine the choice of prosthesis. Treatment planning in general and with respect to individual anatomic-morphologic conditions is described for the upper and lower jaw. Details of clinical procedures with ITI implants related to the specific design of prostheses are presented. Biomechanical aspects of fixation and stabilization of prostheses and aspects of occlusion to be built up complete the overview.

Prosthetic management of the partially dentate patient with fixed implant restorations.

The aim of this chapter is to discuss the current prosthetic management of the partially dentate patient by means of fixed implant restorations in the scope of the ITI(R) Dental Implant System. For that purpose, the related statements defined by the participants of the prosthodontic section of the 1997 ITI Consensus Conference in Vitznau, Switzerland, will be presented, completed by explanatory comments where appropriate. Distinct conceptual differences will be made between the esthetic zone (areas of the dental arches where esthetic considerations are of primary concern) and the non-esthetic zone (regions of the jaws where esthetic aspects do not represent a priority), and between single tooth replacement and multiple unit implant restorations. Furthermore, it is underlined that current clinical concepts should be based on both predictable treatment outcome and cost-effectiveness. In this context, a straightforward surgical and prosthetic protocol is generally preferred in posterior locations of the oral cavity, using a nonsubmerged implant placement comprising an easily accessible implant shoulder location, and subsequently cemented implant restorations, basically according to a traditional prosthodontic approach. In esthetically demanding indications, where normally a distinctly submucosal implant shoulder location is advocated, screw-retained restorations are preferred, based on prefabricated prosthetic components (e.g. machined cast-on copings) to assure optimum surface properties and contour, and to achieve adequate marginal adaptation.

Real-time dissolution measurement of sized and unsized calcium phosphate glass fibers.

The objective of this study was to develop an efficient "real time" measurement system able to directly measure, with microgram resolution, the dissolution rate of absorbable glass fibers, and utilize the system to evaluate the effectiveness of silane-based sizing as a means to delay the fiber dissolution process. The absorbable glass fiber used was calcium phosphate (CaP), with tetramethoxysilane selected as the sizing agent. E-glass fiber was used as a relatively nondegrading control. Both the unsized-CaP and sized-CaP degraded linearly at both the 37 degrees C and 60 degrees C test temperature levels used. No significant decrease in weight-loss rate was recorded when the CaP fiber tows were pretreated, using conventional application methods, with the tetramethoxysilane sizing for either temperature condition. The unsized-CaP and sized-CaP weight loss rates were each significantly higher at 60 than at 37 degrees C (both p < 0.02), as expected from dissolution kinetics. In terms of actual weight loss rate measured using our system for phosphate glass fiber, the unsized-CaP fiber we studied dissolved at a rate of 10.90 x 10(-09) and 41.20 x 10(-09) g/min-cm(2) at 37 degrees C and 60 degrees C, respectively. Considering performance validation of the developed system, the slope of the weight loss vs. time plot for the tested E-glass fiber was not significantly different compared to a slope equal to zero for both test temperatures.

Segregation analysis of Parkinson disease.

Parkinson disease (PD) is a prevalent movement disorder of unknown cause whose incidence rises with increasing age. Nearly 20% of PD is familial, a small subset of which exhibits autosomal dominant transmission. However, in most families, the inheritance is not clear. To determine the most likely mode of inheritance of PD, we performed complex segregation analyses using kindreds of 136 PD patients randomly ascertained from a clinic population. The hypotheses of a nontransmissible environmental factor, no major gene or type (sporadic), and all Mendelian inheritance (dominant, recessive, additive, decreasing) were rejected (P <0.001). Familial clustering of PD in this data set is best explained by a rare familial factor which a) is transmitted in a nonMendelian fashion, and b) influences the age at onset of PD. If confirmed, our results have immediate implications in gene-mapping studies which often search for genes that behave in a Mendelian fashion that affect susceptibility rather than age at onset and long term implications in understanding the pathogenesis of PD.