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Biomedical subjects

D L Wheeler

Publications and source records attributed to D L Wheeler.

At least 19 recordsLinked to original sources

Dietary-induced metabolic acidosis decreases bone mineral density in mature ovariectomized ewes.

Dietary-induced metabolic acidosis (DIMA) may be a significant confounder in the development of osteoporosis. Diets that are acidifying are typically rich in proteins and grains and relatively poor in fruits and vegetables. Previous studies have not examined whether an interaction between estrogen depletion and DIMA have a compounded affect on bone mineral density loss. Sheep have been used successfully in previous studies to examine the interaction of bone turnover and ovariectomy. Therefore, the goal of this pilot study was to determine if bone mineral density (BMD) loss could be induced using DIMA in skeletally mature ovariectomized (OVX) ewes.

Acidosis↗

Quantification methodology for peripheral quantitative computed tomography (PQCT) data using public domain software.

OBJECTIVE: To develop a method for viewing, processing and acquiring 3-dimensional volumetric data from existing ovine spinal peripheral quantitative computed tomography (PQCT) scans of posterior lateral fusion. DESIGN: An image processing development study. BACKGROUND: Existing medical image viewing software can be expensive and difficult to adapt to meet specific research needs. The goals of this study were to produce volume rendering of PQCT scans through processing, masking, and segmentation using public domain software with established source code. METHODS: Raw data files (DICOM format) of 32 PQCT scans from animals receiving spine fusion were obtained. Metal hardware was removed from the images by masks and image segmentation. Calculation of bone macro-architecture volumetric data was performed on right and left sides of spines to quantify fusion volume in normalized segments between transverse processes. RESULTS: Images were acquired and opened. Application of image processing techniques made it possible to remove surgical hardware from original images with minimal loss of original PQCT data. Volumes were calculated and normalized to gray-scale of total bone throughout individual selected segments. CONCLUSION: Using public domain software is a cost effective means to view, process, and manipulate PQCT data. Bone macro-architecture can provide quantitative volumetric contributions to ascertain the role of structure on mechanical function.

Algorithms↗

Assessment of subchondral bone mineral density in equine metacarpophalangeal and stifle joints.

Functional relationships between articular cartilage and underlying subchondral bone have been shown to be associated with the progression of osteoarthritis (OA). However, quantifiable factors substantiating this relationship do not exist. Therefore, the study objective involved quantifying subchondral bone mineral density (BMD) of the equine metacarpophalangeal (MCP) and stifle joints as a step in determining if regional subchondral BMD may be associated with OA changes. BMD was bilaterally quantified using dual energy xray absorptiometry (DEXA) for four subchondral regions: palmer and dorsal aspect of the medial 3rd metacarpal (MC3P, MC3D), medial femoral condyle (MFC), and the medial trochlear ridge (MTR). BMD (g/cm2) was measured using a 5.2 x 5.2 mm region of interest in the subchondral bone area. To account for the differences in thickness, BMD (g/cm2) was divided by sample thickness providing volumetric BMD (g/cm3). No significant effect of side on BMD values was found (p > 0.72). However, there were significant differences in BMD found between all regions (p < 0.05). The volumetric BMD of the MC3P region was significantly greater than the MC3D and the MC3D was greater than the MFC, while the MFC was greater than the MTR (MC3P > MC3D > MFC > MTR). The MCP regions had a higher volumetric BMD than the stifle regions possibly due to higher weight distribution, smaller articular surface area, and joint geometry. The adaptive bone structural variations between the regions studied were shown to be significant. Mechanical properties of the overlying cartilage are currently being analyzed to correlate with these results and provide a possible diagnostic method to investigate OA progression.

Absorptiometry, Photon↗

Relation of the induction of epidermal ornithine decarboxylase and hyperplasia to the different skin tumor-promotion susceptibilities of protein kinase C alpha, -delta and -epsilon transgenic mice.

To define the in vivo role of individual PKC isoforms in mouse skin carcinogenesis, we previously characterized FVB/n transgenic mice that over-expressed epitope-tagged PKC delta (T7-PKC delta) or PKC epsilon (T7-PKC epsilon) isoforms under the regulation of the human K14 promoter. In continuation of our prior PKC isoform specificity studies, we now report the generation of FVB/n transgenic mice with K14-regulated, epitope-tagged PKC alpha (T7-PKC alpha). T7-PKC alpha transgenic mice (line 115) express 8-fold more PKC alpha protein than wild-type mice. Using high-resolution immunogold cytochemistry, we determined that transgenic over-expression of T7-PKC alpha did not alter the subcellular localization of PKC alpha but that the density of PKC alpha staining increased. PKC alpha localized primarily to the cytoskeleton (tonofilaments, tight junctions) and cell membranes, with modest but definite nuclear labeling also identified. Also, PKC alpha over-expression did not alter the immunoreactive protein levels of other PKC isoforms (delta, epsilon, eta, zeta, mu) in the epidermis. Skin tumor-promotion susceptibility was compared among all 3 lines of T7-PKC transgenic mice (alpha, delta and epsilon). While T7-PKC alpha had no effect on skin tumor promotion by TPA, T7-PKC delta reduced papilloma burden by 76% compared to wild-type controls. T7-PKC epsilon further reduced papilloma burden to 93% compared to wild-type controls but still resulted in the development of squamous-cell carcinoma. To find potential mechanisms of PKC-associated differences in tumor promotion, the induction of known downstream effectors of tumor promotion, ornithine decarboxylase (ODC) activity and epidermal hyperplasia, was determined. Despite long-term papilloma inhibition in both PKC delta and PKC epsilon transgenic mice, the induction of ODC by TPA was not attenuated in PKC delta and epsilon mouse lines. Both PKC transgenic and wild-type mice exhibited sustained hyperplasia after repeated TPA treatments. However, TPA-induced epidermal hyperplasia in T7-PKC epsilon mice was significantly increased (52%) compared with T7-PKC alpha, T7-PKC delta and wild-type mice. TPA-induced ODC activity and the resultant accumulation of polyamines may play different roles (e.g., induction of apoptosis vs. proliferation) in the pathways leading to the induction of cancer in PKC alpha, PKC delta and PKC epsilon transgenic mice.

Animals↗

Differential healing response of bone adjacent to porous implants coated with hydroxyapatite and 45S5 bioactive glass.

This study tested the hypothesis that the rate and the extent of bone formation adjacent to porous, coated Ti-6Al-4V implants are differentially affected by the type of bioactive ceramic coating. Forty-eight rabbits received cylindrical Ti-6Al-4V intramedullary distal femoral implants bilaterally. Implants for the right limbs were coated with 45S5 Bioglass (45S5). Implants used for the left limbs either were coated with tricalcium phosphate/hydroxyapatite (HA) or were left uncoated as controls (CTL). The 45S5-coated implants histologically and biomechanically were compared to HA-coated and CTL implants at 4, 8, 12, and 16 weeks. After 12 and 16 weeks of healing, more bone and thicker trabeculae were measured histomorphometrically within the implant pores for the 45S5-coated implants compared to the HA-coated and CTL implants (p < 0.05). With time the HA-coated and CTL groups exhibited a significant decline in percent of bone and of trabecular thickness (p < 0.05) while the 45S5-coated implants did not. Biomechanical analyses indicated similar shear strengths for all treatment groups. In summary, 45S5-coated implants exhibited greater bone ingrowth compared to HA-coated and CTL implants, and they maintained their mechanical integrity over time.

Animals↗

Protein kinase C-epsilon transgenic mice: a unique model for metastatic squamous cell carcinoma.

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common forms of human skin cancer. BCC is slow growing and mostly localized, whereas SCC metastasizes to the regional lymph nodes and subsequently to distal organs. In murine skin carcinogenesis models for SCC, the incidence of metastasis is very low. We report here that FVB/N transgenic mice, which overexpress (approximately 18-fold) epitope-tagged protein kinase C-epsilon (T7-PKCepsilon) protein in the epidermis provide a unique murine model system for highly malignant/metastatic SCC. Skin tumors were developed by the initiation-promotion protocol (initiation with 100 nmol 7,12-dimethyl-benz[a]anthracene; promotion with 5 nmol 12-O-tetradecanoylphorbol-13-acetate twice weekly). T7-PKCepsilon transgenic mice showed 92% suppression of papilloma development compared with wild-type littermates after 23 weeks of tumor promotion. However, within 15-20 weeks of 12-O-tetradecanoylphorbol-13-acetate promotion, 40% of T7-PKCepsilon mice developed at least one carcinoma compared with 7% of the wild-type mice. All carcinomas from T7-PKCepsilon mice appeared without prior papilloma formation. Interestingly, 7,12-dimethyl-benz[a]anthracene alone resulted in the development of squamous cell carcinomas in 22% of T7-PKCepsilon mice, whereas wild-type littermates developed no tumors. Histopathological analysis of tumors from multiple T7-PKCepsilon mice revealed moderately differentiated SCC invading the dermal region with neoplasia appearing to originate and invade from the hair follicle. Carcinomas of T7-PKCepsilon mice rapidly metastasized to regional lymph nodes within 3 weeks of appearance. In wild-type mice, the grade of the invading tumors, originating from interfollicular epidermis, was pathologically categorized as well-differentiated SCC and remained localized to the dermis. The T7-PKCepsilon transgenic mice may provide a rapid and unique in vivo model to investigate metastatic SCC.

9,10-Dimethyl-1,2-benzanthracene↗

Database resources of the National Center for Biotechnology Information.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's Web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomoloGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, GeneMap'99, Human-Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, Cancer Genome Anatomy Project (CGAP), SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheri-tance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih. gov.

Animals↗

Ulnar nerve excursion and strain at the elbow and wrist associated with upper extremity motion.

Significant excursion of the ulnar nerve is required for unimpeded upper extremity motion. This study evaluated the excursion necessary to accommodate common motions of daily living and associated strain on the ulnar nerve. The 2 most common sites of nerve entrapment, the cubital tunnel and the entrance of Guyon's canal, were studied. Five fresh-frozen, thawed transthoracic cadaver specimens (10 arms) were dissected and the nerve was exposed at the elbow and wrist only enough to be marked with a microsuture. Excursion was measured with a laser mounted on a Vernier caliper fixed to the bone and aligned in the direction of nerve motion. A Microstrain (Burlington, VT) DVRT strain device was applied to the nerve at both the elbow and wrist. Nerve excursion associated with motion of the shoulder, elbow, wrist, and fingers (measured by goniometer) was measured at the wrist and elbow. An average of 4.9 mm ulnar nerve excursion was required at the elbow to accommodate shoulder motion from 30 degrees to 110 degrees of abduction, and 5.1 mm was needed for elbow motion from 10 degrees to 90 degrees. When the wrist was moved from 60 degrees of extension to 65 degrees of flexion, 13.6 mm excursion of the ulnar nerve was required at the wrist. When all the motions of the wrist, fingers, elbow, and shoulder were combined, 21.9 mm of ulnar nerve excursion was required at the elbow and 23.2 mm at the wrist. Ulnar nerve strain of 15% or greater was experienced at the elbow with elbow flexion and at the wrist with wrist extension and radial deviation. Any factor that limits excursion at these sites could result in repetitive traction of the nerve and possibly play a role in the pathophysiology of cubital tunnel syndrome or ulnar neuropathy at Guyon's canal.

Cubital Tunnel Syndrome↗

Biomechanical evaluation of retrieved massive allografts: preliminary results.

Allograft bone is the primary source of graft material for large skeletal defects. No study has determined the physical characteristics of such grafts after various periods of time in vivo for incorporation and remodeling. The purpose of this pilot study was to obtain allograft tissue and biomechanically evaluate the tissue to assess allograft bone material properties. The mechanical properties of the retrieved allograft tissue were compared to allograft bone prior to transplantation. Histological analysis of the retrieved allograft tissue is currently underway to correlate degree of incorporation, allograft porosity, and microfracture density with allograft material properties. After allograft retrieval, radiographs were used to plan sectioning for histological and biomechanical analyses. Rectangular sections of uniform dimensions (50 x 3 x 3 mm) were mapped and machined from the bulk specimens. The samples were loaded in bending in the medial to lateral direction using a 4-point bending fixture to obtain flexural elastic modulus and breaking strength. Preconditioning was applied to each specimen by cycling through 5 submaximal loading cycles (maximum deflection = 1% specimen length). After preconditioning, the specimens were loaded to failure at a rate of 1 mm/min. Retrieved specimens consisted of 1 tibia, 2 femurs, and 2 humeri ranging from 2 to 13 years in vivo. Two control tibia specimens were also tested. Assuming that material properties of cortical bone are consistent regardless of skeletal site, the preliminary data indicates that allograft modulus and strength decline with time in vivo. Testing and analysis of more specimens continue in order to corroborate these initial results.

Biomechanical Phenomena↗

Aging regulates 5-HT(1B) receptors and serotonin reuptake sites in the SCN.

Middle age is associated with changes in circadian rhythms (e.g., alterations in the timing of the circadian wheel running rhythm) which resemble changes induced by selective destruction of the serotonergic input to the suprachiasmatic nucleus (SCN), the principal mammalian circadian pacemaker. We hypothesized that serotonergic neurotransmission in the SCN is decreased in middle-aged hamsters, as compared to young adults. This hypothesis was tested indirectly by investigating the effect of aging on two markers of serotonin neurotransmission, 5-HT(1B) receptors and serotonin reuptake sites, which are regulated by serotonin. Previous studies have shown that experimentally induced decreases in serotonergic neurotransmission increase 5-HT(1B) receptors but decrease serotonin reuptake sites. Quantitative autoradiography was conducted using [125I]iodocyanopindolol ([125I]ICYP) and [3H]paroxetine, selective radioligands for the 5-HT(1B) receptors and the serotonin reuptake sites, respectively. Consistent with the hypothesis, specific ([125I]ICYP binding was significantly elevated in the SCN of middle-aged hamsters, as compared to young hamsters. The results also showed that serotonin reuptake sites in the SCN were significantly increased in both middle-aged and old hamsters, as compared to young controls. This result could not have been caused by decreased serotonin release. Alternatively, increased serotonin reuptake, which would reduce serotonin levels in the synaptic cleft, may cause or contribute to the increase in 5-HT(1B) receptor binding in the SCN in middle aged animals. These results show that the SCN exhibits changes in serotonergic function during middle age, which has been characterized by changes in the expression of circadian rhythms. Because these changes occur during middle age, they probably reflect the aging process, rather than senescence or disease.

Aging↗

Database resources of the National Center for Biotechnology Information.

In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval and resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's Web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing pages, GeneMap'99, Davis Human-Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP) pages, Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, Cancer Genome Anatomy Project (CGAP) pages, SAGEmap, Online Mendelian Inheritance in Man (OMIM) and the Molecular Modeling Database (MMDB). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih. gov

Animals↗

GenBank.

The GenBank((R))sequence database incorporates publicly available DNA sequences of >55 000 different organisms, primarily through direct submission of sequence data from individual laboratories and large-scale sequencing projects. Most submissions are made using the BankIt (Web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping and protein structure information, plus the biomedical literature via PubMed. Sequence similarity searching is provided by the BLAST family of programs. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. NCBI also offers a wide range of WWW retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the NCBI home page at http://www.ncbi.nlm.nih.gov

Animals↗

Assessment of resorbable bioactive material for grafting of critical-size cancellous defects.

Bioactive glasses form a surface apatite layer in vivo that enhances the formation and attachment of bone. Sol-gel Bioglass graft material provides greater nanoscale porosity than bioactive glass (on the order of 50-200 A), greater particle surface area, and improved resorbability, while maintaining bioactivity. This study histologically and biomechanically evaluated, in a rabbit model, bone formed within critical-sized distal femoral cancellous bone defects filled with 45S5 Bioglass particulates, 77S sol-gel Bioglass, or 58S sol-gel Bioglass and compared the bone in these defects with normal, intact, untreated cancellous bone and with unfilled defects at 4, 8, and 12 weeks. All grafted defects had more bone within the area than did unfilled controls (p < 0.05). The percentage of bone within the defect was significantly greater for the 45S5 material than for the 58S or 77S material at 4 and 8 weeks (p < 0.05), yet by 12 weeks equivalent amounts of bone were observed for all materials. By 12 weeks, all grafted defects were equivalent to the normal untreated bone. The resorption of 77S and 58S particles was significantly greater than that of 45S5 particles (p < 0.05). Mechanically, the grafted defects had compressive stiffness equivalent to that of normal bone at 4 and 8 weeks. At 12 weeks, 45S5-grafted defects had significantly greater stiffness (p < 0.05). At 8 and 12 weeks, all grafted defects had significantly greater stiffness than unfilled control defects (p < 0.05). In general, the 45S5-filled defects exhibited greater early bone ingrowth than did those filled with 58S or 77S. However, by 12 weeks, the bone ingrowth in each defect was equivalent to each other and to normal bone. The 58S and 77S materials resorbed faster than the 45S5 materials. Mechanically, the compressive characteristics of all grafted defects were equivalent or greater than those of normal bone at all time points.

Animals↗

Glenohumeral kinematics and capsulo-ligamentous strain resulting from laxity exams.

OBJECTIVE: Identification and quantification of strain in shoulder capsular-ligamentous structures during clinical exams and validation of this testing on cadavers. METHODS: Mercury strain gauges were sutured in seven locations on shoulders from cadavers. An electromagnetic tracker quantified humeral head translations during laxity exams. Strain and humeral position were acquired during performance of Sulcus, Feagin, Apprehension, Load and Shift, Drawer, and Hawkins tests. RESULTS: Anterior humeral head translation in neutral position was primarily constrained by the coracohumeral ligament. With the arm abducted, anterior middle and inferior ligaments also became active. External rotation and abduction activated inferior and middle capsules. Posterior capsule constrained motion for posterior tests in neutral and abduction. Superior and inferior capsular ligaments were active during inferior tests in neutral position. With abduction, inferior ligaments provided primary translation constraint. CONCLUSION: Study of kinematics and strain evaluation on cadavers can yield useful information on mechanisms of glenohumeral instability. Relevance This study clarifies the contribution of specific structures of the shoulder to strain in the joint capsule. It also identifies which structures are challenged by provocative laxity exams commonly used by orthopaedic physicians.

Analysis of Variance↗

Mechanical strength of fracture callus in osteopenic bone at different phases of healing.

OBJECTIVES: To quantify and compare peak bending force and stiffness of fractured femurs during healing of ovariectomized (OVX) and sham-operated (SHAM) rats. DESIGN: Temporal biomechanical animal study. SETTING: Rat femurs were fractured and surgically fixed by a qualified surgeon. The inherent instability of the fixation system employed produced delayed union of the fracture. All biomechanical assessments were performed with servohydraulic test machines (Instron Inc., Canton, MA, U.S.A.; and MTS Corp., Eden Prairie, MN, U.S.A.). INTERVENTION: OVX was performed sixteen weeks before femur fracture, and the effect of OVX on healing fractures was determined. MAIN OUTCOMES: Peak bending force and stiffness of the healing femurs at four, six, and eight weeks after fracture. RESULTS: Peak bending loads of the healing fractured femurs in the OVX and SHAM animals were not significantly different. Peak bending loads for the OVX animals at four and six weeks were significantly lower than the peak load at eight weeks (p < 0.05), whereas no difference was found in the peak load with respect to time for the SHAM animals. Both SHAM and OVX animals had greater bending stiffness of the healing fractured femur after eight weeks of healing than at four weeks (p < 0.05). CONCLUSIONS: OVX is known to reduce cancellous bone mass and strength, but the effect of OVX on healing of fractures in cortical bone is controversial. This study, using a delayed-union model, found no significant differences between OVX and SHAM animals in the breaking strength of healing fractures.

Animals↗

Aging and photoperiod regulate glutamic acid decarboxylase(67) messenger RNA expression.

Aging and short photoperiod exposure both induce similar long-term changes in circadian rhythms, including alterations in the timing and the amplitude of rhythms. Furthermore, these chronic conditions affect the function of the circadian pacemaker in the suprachiasmatic nuclei (SCN) by altering rhythmic expression of neuropeptide messenger RNAs (mRNAs). Because GABA modulates SCN neuronal activity, and GABAergic neurons innervate peptidergic neurons in the SCN, the present study investigated whether photoperiod or aging affect the expression of mRNA for GAD(67), the enzyme responsible for regulating the tonic levels of GABA. As a control for regional specificity, the reticular thalamic nucleus (RTN) was also examined. In situ hybridization for GAD(67) mRNA was performed on brain sections derived from Siberian hamsters exposed to a long day or a short day photoperiod for 15 days, and on brain sections from young (3-4 months old) and old (12-17 months old) Syrian hamsters exposed to a long photoperiod. The results showed that photoperiod and aging have different effects on GAD(67) mRNA expression. Exposure to short day photoperiod significantly increased GAD(67) mRNA expression in both the SCN and RTN of Siberian hamsters, while aging significantly decreased GAD(67) mRNA expression in the RTN of Syrian hamsters but had no effect on GAD(67) mRNA expression in the SCN. These findings suggest that modulation of GAD(67) mRNA expression in the SCN is associated with photoperiodic regulation of neuropeptide mRNA expression, but is not a common mechanism for chronic regulation of circadian rhythms. Also, GAD(67) mRNA expression in the RTN is differentially affected by photoperiod and aging.

Aging↗

Comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters.

The circadian timekeeping system exhibits many functional changes with aging, including a loss of sensitivity to time cues such as systemic injections of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to elucidate the neurochemical mechanisms responsible for this age-related loss of sensitivity of the circadian pacemaker to serotonin agonists, the present study used quantitative autoradiography to determine whether aging decreases serotonin receptor populations in male Syrian hamsters. Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [SCN], the lateral geniculate nuclei [LGN], and the median raphe nucleus [MRN] and dorsal raphe nucleus [DRN]). The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. The results showed that the SCN, IGL, MRN, and DRN of the male Syrian hamster exhibited specific binding of [3H]8-OH-DPAT to both the 5-HT7 and 5-HT1A receptors, and that the latter receptor subtype is more abundant in all of these regions. At 17-19 months of age, a 50% decrease in 5-HT7 receptors was found in the DRN but not in any other regions. No significant age-related changes in 5-HT1A receptors were observed in any regions examined. The finding that a marked decrease in 5-HT7 receptors occurs in the DRN at the age previously characterized by loss of sensitivity to 8-OH-DPAT suggests that this region and this receptor subtype play important roles in 8-OH-DPAT induction of circadian phase shifts in vivo and that they constitute an important locus of aging in the circadian timing system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

GenBank.

The GenBank (Registered Trademark symbol) sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from individual laboratories and from large-scale sequencing projects. Most submitters use the BankIt (Web) or Sequin programs to format and send sequence data. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome and protein structure information. MEDLINE (Registered Trademark symbol) s from published articles describing the sequences are included as an additional source of biological annotation through the PubMed search system. Sequence similarity searching is offered through the BLAST series of database search programs. In addition to FTP, Email, and server/client versions of Entrez and BLAST, NCBI offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the URL: http://www.ncbi.nlm.nih.gov

Amino Acid Sequence↗