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Biomedical subjects

M D Miller

Publications and source records attributed to M D Miller.

At least 127 records · Page 7Linked to original sources
PubMed1995

Skeletal muscle injuries.

Muscular injuries are extremely common in athletes. Treatment of these injuries is based on a solid understanding of anatomy, physiology, and healing of skeletal muscle. Injuries discussed include contusions, hematomas, myositis ossificans, delayed onset soreness, strain, rhabdomyolysis, and lacerations. Diagnosis and treatment of these injuries is essential for the sports medicine physician.

Contusions↗
PubMed1994

The human immunodeficiency virus-1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages.

Considerable controversy and uncertainty have surrounded the biological function of the Human Immunodeficiency Virus (HIV)-1 nef gene product. Initial studies suggested that this early, nonstructural viral protein functioned as a negative regulatory factor; thus, it was proposed to play a role in establishing or maintaining viral latency. In contrast, studies in Simian Immunodeficiency Virus (SIV)mac-infected rhesus monkeys have suggested that Nef is not a negative factor but rather plays a central role in promoting high-level viral replication and is required for viral pathogenesis in vivo. We sought to define a tissue culture system that would approximate the in vivo setting for virus infection in order to assess the role of HIV-1 Nef in viral replication. We show that infection of mitogen-activated peripheral blood mononuclear cells (PBMC) with Nef+ HIV results in enhanced replication as evidenced by earlier gag p24 expression when compared with infections performed with nef mutant viruses. Moreover, when unstimulated freshly isolated PBMC are infected with Nef+ and Nef- viruses and then subsequently activated with mitogen, the Nef-induced difference in viral replication kinetics is even more pronounced, with the Nef- viruses requiring much more time in culture for appreciable growth. A positive effect of Nef on viral replication was also observed in primary macrophages infected with a recombinant of YU-2, a patient-derived molecular clone with macrophage tropism. These positive effects of Nef on viral replication are dependent on the initial multiplicity of infection (MOI), in that infections of unstimulated PBMC at low MOI are most dependent upon intact nef for subsequent viral growth. We now provide evidence that the Nef+ HIV is more infectious than Nef- HIV from both a tissue culture infectious dose analysis, and a single-cell HIV infection assay. In the latter case, we demonstrate that infection with equivalent doses of HIV based on virion-associated gag p24 yields five- to sixfold more infected cells if Nef+ viral stocks were used. Furthermore, we find that the differential infectivity is not dependent on CD4 down-regulation as Nef+ virus produced from transfected COS cells lacking CD4 is also more infectious. However, normalization of PBMC infections to equivalent infectivity between that of the Nef+ and Nef- viruses continues to reveal delayed viral replication in the absence of Nef, suggesting that secondary viral spread in PBMC is also enhanced in Nef+ infections. We demonstrate this directly by showing a 13-15-fold increase in infectivity of PBMC-derived Nef+ HIC.(ABSTRACT TRUNCATED AT 400 WORDS)

CD4 Antigens↗
PubMed1994

FLOG: a system to select 'quasi-flexible' ligands complementary to a receptor of known three-dimensional structure.

We present a system, FLOG (Flexible Ligands Oriented on Grid), that searches a database of 3D coordinates to find molecules complementary to a macromolecular receptor of known 3D structure. The philosophy of FLOG is similar to that reported for DOCK [Shoichet, B.K. et al., J. Comput. Chem., 13 (1992) 380]. In common with that system, we use a match center representation of the volume of the binding cavity and we use a clique-finding algorithm to generate trial orientations of each candidate ligand in the binding site. Also we use a grid representation of the receptor to assess the fit of each orientation. We have introduced a number of novel features within this paradigm. First, we address ligand flexibility by including up to 25 explicit conformations of each structure in our databases. Nonhydrogen atoms in each database entry are assigned one of seven atom types (anion, cation, donor, acceptor, polar, hydrophobic and other) based on their local bonded chemical environments. Second, we have devised a new grid-based scoring function compatible with this 'heavy atom' representation of the ligands. This includes several potentials (electrostatic, hydrogen bonding, hydrophobic and van der Waals) calculated from the location of the receptor atoms. Third, we have improved the fitting stage of the search. Initial dockings are generated with a more efficient clique-finding algorithm. This new algorithm includes the concept of 'essential points', match centers that must be paired with a ligand atom. Also, we introduce the use of a rapid simplex-based rigid-body optimizer to refine the orientations. We demonstrate, using dihydrofolate reductase as a sample receptor, that the FLOG system can select known inhibitors from a large database of drug-like compounds.

Algorithms↗
PubMed1994

Flexibases: a way to enhance the use of molecular docking methods.

Specially expanded databases containing three-dimensional structures are created to enhance the utility of docking methods to find new leads, i.e., active compounds of pharmacological interest. The expansion is based on the automatic generation of a set of maximally dissimilar conformations. The ligand receptor system of methotrexate and dihydrofolate reductase is used to demonstrate the feasibility of creating flexibases and their utility in docking studies.

Algorithms↗
PubMed1994

Residues of p,p'-DDE in lake trout in Little Moose Lake in New York State.

Residues of p,p'-DDE were found in lake trout sampled in 1993 from Little Moose Lake located remotely in the Adirondack region of New York State. Length accounted for 81% of the variation in p,p'-DDE concentration when the data was fit to an exponential model. The presence of p,p'-DDE in the fish was believed due to its long persistence in the aquatic environment following applications of DDT in the 1950s for control of black flies and mosquitoes.

Animals↗
PubMed1994

Munchausen syndrome by proxy: unusual manifestations and disturbing sequelae.

Since the initial description of Munchausen Syndrome by Proxy (MSBP) (Meadow, 1977), numerous cases have been reported varying from as simple as the complaint of a nonexistent symptom to those as complicated as altered laboratory tests leading to the false diagnosis of cystic fibrosis (Orenstein & Wasserman, 1986; Rosenberg, 1987). We report three findings previously unreported: esophageal perforation, retrograde intussusception, and tooth loss. Bradycardia has been previously reported associated with suffocation (Meadow, 1984), but in our case may have been caused by carotid artery massage. We also suggest possible induction by the mother of premature rupture of fetal membrane leading to delivery of infected infants.

Bradycardia↗
PubMed1994

The HIV-1 nef gene acts as a positive viral infectivity factor.

The gene product of the nef gene of HIV-1 acts both to increase the infectivity of viral particles and to reduce the expression of the CD4 receptor molecule on the cell surface. These two functions of Nef may be related, in that downregulation of CD4 may promote the production of HIV that has greater infectivity.

Animals↗
PubMed1994

Repetition blindness and aging: evidence for a binding deficit involving a single, theoretically specified connection.

This study tested 2 main hypotheses for explaining repetition blindness (RB), a difficulty in encoding and recalling rapidly presented repeated words in sentences. Under 1 hypothesis, RB reflects an inhibitory process and should be more pronounced in young than in older Ss, who typically exhibit diminished inhibitory processes. Under the second hypothesis, RB reflects a failure to bind a specific connection: The second connection from the single node for encoding a repeated word is difficult to form under time pressure. Under this binding hypothesis, young adults should exhibit less RB than older adults, who typically require more time to form new connections. Results supported a version of the binding hypothesis but contradicted the inhibition hypothesis, and did not support hypotheses whereby RB reflects either a refractory effect or perceptual fusion of the repeated words.

Adult↗
PubMed1994

2.1 A structure of Serratia endonuclease suggests a mechanism for binding to double-stranded DNA.

The crystal structure of Serratia endonuclease has been solved to 2.1 A by multiple isomorphous replacement. This magnesium-dependent enzyme is equally active against single- and double-stranded DNA, as well as RNA, without any apparent base preference. The Serratia endonuclease fold is distinct from that of other nucleases that have been solved by X-ray diffraction. The refined structure consists of a central layer containing six antiparallel beta-strands which is flanked on one side by a helical domain and on the opposite side by one dominant helix and a very long coiled loop. Electrostatic calculations reveal a strongly polarized molecular surface and suggest that a cleft between this long helix and loop, near His 89, may contain the active site of the enzyme.

Amino Acid Sequence↗
PubMed1994

Biodegradable, effective substitute for xylene in the Ehrlich indole procedure.

Three extracting reagents were compared for effectiveness in the Ehrlich indole procedure: xylene (the recommended reagent), Hemo-De (a terpene-based product containing d-limonene), and Micro-Clear (an isoparaffinic hydrocarbon). Thirty-three strains representing 12 species of indole-positive aerobes or facultative anaerobes and 50 strains representing 11 species of indole-positive strict anaerobes were tested using the three reagents. Xylene extraction allowed indole detection in all of the isolates tested. Micro-Clear allowed detection in all of the aerobic isolates and in 49 of 50 anaerobes. Hemo-De allowed indole detection in 32 of 33 aerobes and in 49 of 50 anaerobes. There was no significant difference in the results among the reagents. Because Micro-Clear is biodegradable, nonflammable, noncarcinogenic, and odorless, we feel that this product should be considered a safe and effective substitute for xylene in the Ehrlich indole procedure.

Bacterial Typing Techniques↗
PubMed1994

Treatment of consecutive episodes of major depression in the elderly.

OBJECTIVE: The purpose of this study was to determine treatment outcome in elderly patients with consecutively treated episodes of recurrent unipolar major depression. METHOD: Subjects were 32 "young" elderly patients with recurrent unipolar depression (mean age = 66.8 years, SD = 5.1) and with two consecutively treated episodes of major depression. Both index and subsequent episodes of major depression were treated in open trial with combined nortriptyline and interpersonal psychotherapy. Rates of remission in index and subsequent episodes were compared by using nonparametric statistics and survival analysis with proportional hazards modeling. RESULTS: Of 30 patients who completed treatment of the subsequent episode, 27 (90%) achieved stable remission of symptoms in both consecutively treated episodes, whereas three patients (10%) did not. Twenty-two (81%) of 27 patients who responded to treatment had a shorter time to remission in treatment of the subsequent episode than in the index episode. Survival analysis with proportional hazards modeling detected a significant difference in time to remission of the index and subsequent episodes (32 paired observations). CONCLUSIONS: In this research study group, recurrent episodes of unipolar major depression in the young elderly were successfully treated to remission in over 80% of patients by using combined pharmacotherapy and psychotherapy similar to that employed in treatment of the index episode. Remission rate and time to remission in consecutively treated episodes were comparable to those in a group of midlife patients with recurrent depression reported by Kupfer et al. in 1989. Thus, recurrent depressive disorder appears to be as treatable in the young elderly as it is in midlife patients.

Age Factors↗
PubMed1994

Colposcopy and cervical biopsy educational training models.

BACKGROUND: Realistic simulation models serve meaningful educational purposes. The intent of this article is to review the physical and educational features of three instructional colposcopy models, and to discuss the advantages and implications of the use of models in teaching colposcopic skills. METHODS: Models made from latex, steak, and the bovine cervix were assessed as instructional devices to simulate the uterine cervix and cervical disease. Model construction, preparation, and unique features were critiqued. The models were also evaluated for their potential use in the preclinical teaching of important colposcopic skills. RESULTS: The latex model required minimal assembly but was costly. It was limited in design, which would exclude the training of most colposcopic techniques. The steak model used readily available materials, facilitated colposcopic skill acquisition, and was the least expensive model. The bovine model best simulated human cervical tissue, was intermediate in cost, and enabled teaching a variety of colposcopic procedures. The optional silicone inserts realistically demonstrated the spectrum of cervical disease. CONCLUSIONS: Various cervical biopsy models have different strengths and weaknesses for teaching colposcopic procedural skills. Available models each possess unique features designed to reproduce anatomy, pathology, tissue texture, and technical spatial limitations. The models permit assessment of gynecologic knowledge and psychomotor abilities.

Animals↗