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Biomedical subjects

D L Hoffman

Publications and source records attributed to D L Hoffman.

At least 19 recordsLinked to original sources

A linkage map of hexaploid oat based on grass anchor DNA clones and its relationship to other oat maps.

A cultivated oat linkage map was developed using a recombinant inbred population of 136 F6:7 lines from the cross 'Ogle' x 'TAM O-301'. A total of 441 marker loci, including 355 restriction fragment length polymorphism (RFLP) markers, 40 amplified fragment length polymorphisms (AFLPs), 22 random amplified polymorphic DNAs (RAPDs), 7 sequence-tagged sites (STSs), 1 simple sequence repeat (SSR), 12 isozyme loci, and 4 discrete morphological traits, was mapped. Fifteen loci remained unlinked, and 426 loci produced 34 linkage groups (with 2-43 loci each) spanning 2049 cM of the oat genome (from 4.2 to 174.0 cM per group). Comparisons with other Avena maps revealed 35 genome regions syntenic between hexaploid maps and 16-34 regions conserved between diploid and hexaploid maps. Those portions of hexaploid oat maps that could be compared were completely conserved. Considerable conservation of diploid genome regions on the hexaploid map also was observed (89-95%); however, at the whole-chromosome level, colinearity was much lower. Comparisons among linkage groups, both within and among Avena mapping populations, revealed several putative homoeologous linkage group sets as well as some linkage groups composed of segments from different homoeologous groups. The relationships between many Avena linkage groups remain uncertain, however, due to incomplete coverage by comparative markers and to complications introduced by genomic duplications and rearrangements.

Avena↗

Profile changes associated with maxillary incisor retraction in the postadolescent orthodontic patient.

Maxillary incisor retraction and associated upper lip changes were studied in 30 male and 30 female postadolescent orthodontic patients to determine if a statistically significant correlation and ratio existed between maxillary incisor and lip retraction, dependent on thickness, strain, and length of the upper lip. This analysis attempted to eliminate the effects of growth and gender. Statistically significant correlations were found in both male and female patients who had thin, highly strained lips. Although a ratio for predictive purposes was determined for each of these groups, their absolute value is questionable because no apparent pattern exists between them. Furthermore, as lip thickness increased and lip strain decreased, correlation coefficients fell to nonsignificance, making it more difficult to predict upper lip change resulting from maxillary incisor retraction in these individuals.

Adult↗

BioSCAN: a network sharable computational resource for searching biosequence databases.

We describe a network sharable, interactive computational tool for rapid and sensitive search and analysis of biomolecular sequence databases such as GenBank, GenPept, Protein Identification Resource, and SWISS-PROT. The resource is accessible via the World Wide Web using popular client software such as Mosaic and Netscape. The client software is freely available on a number of computing platforms including Macintosh, IBM-PC, and Unix workstations.

Algorithms↗

Pseudotorsional OCCO backbone angle as a single descriptor of protein secondary structure.

Protein secondary structure is conventionally identified using characteristic ranges of two backbone torsional angles phi and psi. We suggest that the secondary structure can be adequately characterized by a single descriptor, the Oi-1Ci-1CiOi (where i is the residue number) pseudotorsional backbone angle. A set of 102 structurally distinct protein chains from the Protein Data Bank was used to evaluate the adequacy of this descriptor. We find that a specific range of OCCO angles corresponds to each major secondary structure. The complete range of OCCO angles (-180 degrees to 179 degrees) was broken into 18 consecutive subranges of 20 degrees each, and each subrange was assigned a letter. Thus, the OCCO profiles for each protein in the database were "translated" into a sequence of letters. The Needleman-Wunsch primary sequence alignment algorithm was then used for secondary/tertiary structure comparison and alignment. Preliminary results indicate that this new approach has a significant potential for rapid identification of fold families in the Protein Data Bank.

Amino Acid Sequence↗

Rapid protein structure classification using one-dimensional structure profiles on the bioSCAN parallel computer.

Rapid growth of protein structures database in recent years requires an effective approach for objective comparison and classification of deposited protein structures. We describe a novel method for structure comparison and classification based on the alignment of one-dimensional structure profiles. These profiles are obtained by calculating the OCCO pseudodihedral angles (formed by O-C-C-O atoms of carbonyl groups of consecutive amino acid residues) from protein three-dimensional coordinates. These angle measurements are then converted into a 24 letter alphabet, and the protein structures are represented by sequences of letter from this alphabet. The BioSCAN parallel computer, designed for primary sequence alignment, is used to rapidly align and classify these one-dimensional structure profiles. We have developed and implemented weighted scoring matrix to identify structural classes based on commonly found structural motifs. The results of our experiments are in good agreement with the traditional protein structure classification schemes. One-dimensional structure profiles significantly improve efficiency of structure comparison and classification.

Algorithms↗

Autorotation test abnormalities of the horizontal and vertical vestibulo-ocular reflexes in panic disorder.

Patients with panic disorder often describe dizziness as a disturbing symptom, with more severe episodes reported than in other psychiatric populations. Nineteen patients diagnosed as having a panic disorder were tested for vestibulo-ocular (VOR) abnormalities with the Vestibular Autorotation Test (VAT), a computerized test of the high-frequency (2 to 6 Hz) VOR. The patients were unselected for the presence or absence of balance disorders. Results showed VOR abnormalities, relative to a normal population, in the horizontal and/or vertical VORs of all 19 patients. Vestibulo-ocular reflex asymmetries were commonly present. Because the VAT tested the VOR over a frequency range encountered during common daily activities, the observed abnormalities could result in a perceptually moving visual field (oscillopsia). We hypothesize that the resulting experience of a visual-vestibular disturbance--perhaps in a biologically or psychologically predisposed individual--is catastrophically misinterpreted, leading to more bodily symptoms and anxiety. These could then contribute to more misinterpretation in a positive feedback sense, ultimately leading to a panic attack.

Adult↗

Encephalopathy, myelopathy, optic neuropathy, and anosmia associated with intravenous cytosine arabinoside.

Coma, hemiparesis, unilateral optic neuropathy, and anosmia manifested in a patient with leukemia after he received only three courses of intravenous high-dose cytosine arabinoside (ARA-C). The patient's mental status returned to normal after several days, and his hemiparesis resolved. However, the visual loss persisted, and near complete visual loss in the other eye ensued over the following month. Severe bilateral optic atrophy appeared as the visual loss progressed. Anosmia became evident after resolution of the coma and did not improve. The patient had previously had a thoracic myelopathy 2 weeks after receiving low-dose i.v. ARA-C. The neurotoxicity of high-dose i.v. ARA-C may arise at much lower cumulative doses than has been reported. In addition to cerebellar dysfunction and somnolence, high-dose i.v. ARA-C may produce optic neuropathy, anosmia, and hemiparesis.

Adult↗

Purification and large-scale preparation of antithrombin III.

Cutter Biological, Miles Inc., has implemented large-scale isolation and purification of antithrombin III (ATIII) from human blood plasma. The starting material, Cohn fraction IV-1, is suspended and ATIII separated from other proteins by heparin-affinity chromatography. The concentrate is subsequently heated for 10 hours at 60 degrees C in a solution of 0.5 M sodium citrate to inactivate the causative agents of viral hepatitis B and acquired immune deficiency syndrome. After heating, a second heparin-affinity chromatography step is employed to isolate the active ATIII and to remove heat-denatured protein. The purified solution is compounded with 0.1 M alanine and 0.15 M sodium chloride, filled in vials of 500 or 1,000 IU each, and freeze dried. The final product has a specific activity of not less than 6.4 IU ATIII per mg protein, of which over 90 percent binds to heparin on crossed immunoelectrophoresis. Preclinical and clinical testing have shown this product to be safe for prophylactic and therapeutic administration to persons with congenital deficiency of ATIII.

Antithrombin III↗

Healing of skin incision wounds treated with topically applied BAPN free base in the rat.

beta-Aminopropionitrile as free base (BAPN) was applied onto the incised or intact skin of rats at the dose of 5, 20, 100, and 200 microliters for 9 days, twice daily. Breaking strength of the skin wound or intact skin was significantly reduced at doses of 20 microliters and higher; body weight growth was significantly retarded at the two highest dosages. It is concluded that at a given dose (20 microliters) collagen polymerization (evaluated by reduced breaking strength and increased extractability of collagen) was specifically inhibited by BAPN. Furthermore, no evidence of topical or general toxic effects were observed, as reflected in histology, body weight growth, and behavior of the rats. Acute LD50 of BAPN base and fumarate, administered either ip or topically, was determined in mice. While BAPN base in ip administration shows LD50 of 1.15 g/kg, in cutaneous application it is more than 12.8 g/kg. It is suggested that topically applied BAPN base is percutaneously absorbed and affects collagen polymerization in the skin and adjacent tissues.

Administration, Topical↗

Histologic analysis of temporomandibular joint adaptation to protrusive function in young adult rhesus monkeys (Macaca mulatta).

It is generally believed that the adult temporomandibular joint is incapable of a significant adaptive response to forces produced by functional jaw orthopedics. To evaluate this view, twelve young adult female rhesus monkeys were fitted with functional protrusive appliances for periods ranging from 2 to 24 weeks. Histologic analysis of the temporomandibular joint demonstrated that six of the experimental animals exhibited a tissue response that was qualitatively similar to that noted in juvenile animals. However, the response in young adults was greatly reduced in magnitude from that seen in juveniles and was not related to duration of treatment. It must also be noted that three adult animals developed cross-bites in response to appliance placement, and three animals who functioned anteriorly exhibited little or no detectable condylar response. This study indicates that while some adaptive capability may still be present in the temporomandibular joints of young adults, the potential magnitude of the joint response is limited and highly variable in occurrence.

Activator Appliances↗

The descending afferent connections of the paraventricular nucleus of the hypothalamus (PVN).

The distribution of afferents to the paraventricular nucleus of the hypothalamus (PVN) was studied following iontophoresis of horseradish peroxidase (HRP) into the nucleus. This report describes the descending connections to this structure. The PVN receives a substantial input from limbic system structures, especially from the lateral septal nucleus and the ventral portion of the subicular cortex. A small number of labeled cells were found in the amygdala, primarily the medial nucleus. Of the circumventricular organs, the subfornical organ and OVLT both project to the PVN, the former very strongly. In both the preoptic area and hypothalamus, medial cell groups have more input than do the lateral areas. Labeled cells were found in the medial and hypothalamus, medial cell groups have more input than do the lateral areas. Labeled cells were found in the medial and lateral preoptic areas, suprachiasmatic nucleus, ventromedial nucleus, arcuate nucleus, retrochiasmatic and lateral hypothalamic areas. Of particular interest is the finding that the PVN receives input from the contralateral PVN and ipsilateral SON. Of the other diencephalic structures only the zone incerta showed a consistent number of labeled cells. The results are discussed in relationship to the possible neural structures that might mediate the response of the PVN neurons to adrenalectomy.

Afferent Pathways↗

Vasopressin concentrations in hypophysial portal plasma: insignificant reduction following removal of the posterior pituitary gland.

This study was designed to determine the relative contribution of vasopressin-secreting nerve terminals in the median eminence compared to those in posterior pituitary to the high concentrations of the hormone in hypophysial portal blood. Vasopressin was measured by radioimmunoassay in plasma obtained by microcannulation of individual long portal veins of 8 intact male Long-Evans rats (2.0 +/- 0.44 ng/ml SEM), and in 8 in which the posterior pituitary was removed just prior to collection (1.5 +/- 0.3 ng/ml SEM). Since there was no significant difference /p = 0.23, NS) in the concentration of vasopressin in portal plasma after removal of the posterior pituitary gland, these results suggest that the direct vasopressin pathway to the median eminence is the major source of vasopressin in portal blood of the rat.

Animals↗