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Biomedical subjects

D Miller

Publications and source records attributed to D Miller.

At least 289 records · Page 16Linked to original sources
PubMed1995

Speech pattern audiometry for clinical use.

A new PC-based speech perception testing system ('speech pattern audiometer') is described which aims to provide a simple and efficient clinical tool to assess patients' ability to make use of the acoustic speech pattern information which is fundamental to speech perception. The speech pattern audiometer is likely to find its main application in audiology and speech and language therapy clinics with those who are deaf or who have developmental or acquired speech-perceptual disorders. This system constitutes a module of a complete speech and hearing assessment and teaching/therapy workstation.

Audiometry, Speech↗
PubMed1995

Inhibition of T lymphocyte activation by a novel p56lck tyrosine kinase inhibitor.

A new p56lck tyrosine kinase inhibitor WIN 61651 [1,4-dihydro-7-(4-methyl-1-piperizinyl)-1-(4-(4-methyl-1-piperi zinyl))phenyl- 4-oxo-3-quinolinecarboxamide) is described. WIN 61651, which is competitive with ATP, demonstrates selectivity for the lymphoid restricted tyrosine kinase p56lck over serine/threonine kinases, such as protein kinase C and protein kinase A, and over some other tyrosine kinases, including erbB2, epidermal growth factor receptor, and insulin receptor; however, it is equipotent for inhibition of p56lck and the platelet derived growth factor receptor tyrosine kinases. WIN 61651 inhibits p56lck activity in cell-free assays, tyrosine kinase activity in a T lymphocytic cell line, and T cell activation, as measured by IL-2 production by purified CD4 positive peripheral blood T lymphocytes and the mixed lymphocyte reaction. WIN 61651 constitutes a new tool for studies on the role for tyrosine kinases in lymphocyte function.

Antibodies↗
PubMed1995

Cost and utilisation of community services for people with HIV infection in London.

This study aimed to describe the use and costs of community services for HIV-infected people by disease stage, sex and transmission category (homosexual, heterosexual, injecting drug use) by use of a prospective cohort study in which people were followed up for six months. There were two major components; gathering quantitative information on service utilisation from people with HIV infection using two interviewer-administered questionnaires and six self-completed monthly diaries; and estimating the costs of the services provided. People were recruited from two London clinics: the Jefferiss Wing Genito-urinary Medicine (GUM) clinic at St. Mary's Hospital, Paddington, and the Patrick Clements GUM clinic at the Central Middlesex Hospital, Harlesden. Costing data was obtained from providers of community services throughout Greater London. The main outcome measures were contacts per person-year, and costs per person-year, for all community services stratified by service sector. The people studied each made, on average, 139 community service contacts per year at a cost of 2,806 pounds; there was little difference in average utilisation between the three transmission categories. There were differences in both the utilisation of services and costs within the formal and informal sectors for subjects from different disease stages. Although the average number of contacts per person-year were similar for women and men, the total cost of community services was higher for women than for men, reflecting the differences in types of services used. The results indicated a high proportion of total care costs for people with HIV and AIDS is incurred through community-based social care.(ABSTRACT TRUNCATED AT 250 WORDS)

Community Health Services↗
PubMed1995

WIN 17317-3: novel nonpeptide antagonist of voltage-activated K+ channels in human T lymphocytes.

We report the in vitro biological characterization of WIN 17317-3 (1-benzyl-7-chloro-4-n-propylimino-1,4-dihydroquinoline hydrochloride), a novel inhibitor of voltage-activated (n-type) K+ channels in human T lymphocytes. WIN 17317-3 inhibits 125I-charybdotoxin binding to n-type K+ channels with an IC50 value of 83 +/- 4 nM. WIN 17317-3 demonstrates competitive inhibition of 125I-charybdotoxin binding by increasing its dissociation constant without changing the total number of channels bound and by having no effect on its dissociation rate constant. WIN 17317-3 inhibits whole-cell, n-type K+ currents with characteristics indicative of open channel block and has an IC50 value of 335 nM. The compound is 150-fold selective for n-type K+ channels, compared with Ca(2+)-activated, charybdotoxin-sensitive K+ channels in smooth muscle. In purified CD4+ T lymphocytes activated with either anti-CD3 plus phorbol ester or anti-CD3 plus anti-CD28, WIN 17317-3 decreases interleukin-2 production with EC50 values of 0.8 microM and 1 microM, respectively. WIN 17317-3 is a novel, potent, and selective nonpeptide n-type K+ channel antagonist that inhibits interleukin-2 production in human T lymphocytes.

Cell Line↗
PubMed1995

Diagnostic assessment and therapeutic approaches to borderline disorders in adolescents.

Not all young people who present with a borderline syndrome are equally vulnerable. Clinical manifestations appear along a spectrum that varies from an apparently less severely disturbed psychoneurotic to those who appear with almost total ego fragmentation (Giovacchini, 1964). When the syndrome appears as a result of social system trauma in early adolescence, adequate diagnosis and appropriate intervention can make for speedy recovery. A typical scenario is the absence of a peer group that is developmentally needed, along with the family tension and social system turbulence produced by a change of location, school, or cultural environment. When executives move with their families, for example, their adolescent children are likely to react with at least depression, with at worst a borderline syndrome. The therapy of disturbed borderline young people is likely to be successful only in an environment that optimally meets developmental needs with skilled intervention in biological, psychological, and social fields. The latter should include work with the family in which the individual psychopathology of the parents, their marital relationships, and the strengths and weaknesses of the family system are all assessed.

Adolescent↗
PubMed1995

Adolescent female offenders: unique considerations.

Profiles of adolescent female offenders in the literature suggest that these women have unique needs. Descriptions of selected characteristics and assessment considerations related to adolescent female offenders were synthesized from relevant research. Recommendations are discussed that propose changing educational programming in order to make curriculum, assessment, methods, and service delivery more responsive to the specific needs of these adolescents.

Adolescent↗
PubMed1995

Adenovirus epithelial keratitis.

The authors sought to determine whether adenovirus could infect human corneal epithelium in vivo. They reviewed the medical records of six patients with adenovirus-positive viral corneal cultures who were examined at the Bascom Palmer Eye Institute between March 21, 1986, and December 31, 1992. The six patients with adenovirus-positive viral corneal cultures included one patient with dendritic epithelial keratitis, one with geographic epithelial ulceration, three with both geographic ulceration and contiguous dendrites, and one with heaped-up corneal epithelium but no ulceration. Four patients had rose bengal solution applied to their ocular surface, and in all four patients rose bengal uptake was seen at the epithelial edges of the dendrite or geographic ulceration in a manner characteristic of herpes simplex viral keratitis. Serotype determination of the isolates showed adenovirus type 3 (one patient), type 8 (three patients), type 19 (one patient), and indeterminate (one patient). Results of monoclonal antibody staining of cultures against herpes simplex virus (types 1 and 2) antigens was negative for all six cases. Adenovirus epithelial keratitis may result from infection of human corneal epithelium by the virus and rarely may mimic infection of corneal epithelium by herpes simplex virus.

Adenovirus Infections, Human↗
PubMed1995

Health care delivery reorganization innovative outcome: universal computerized patient identification.

Twenty-three large employers in the Minneapolis/St. Paul area formed the business health care action coalition group (BHCAC) to obtain medical care for their employees and families. Requirements of BHCAC included: 1) detailed reporting of outcomes of both preventive and standard health care, 2) development and successful implementation of practice guidelines, and 3) development of a functioning automated medical record. The coalition was contracted to meet these requirements. A nonprofit foundation--the Institute for Clinical Systems Integration (ICSI)--was formed and the data standards committee created. To ensure registration information transmitted by network would be attached to the correct patient's computer file; a standardized registration data set was agreed upon to be recorded in a uniform manner. This innovative change has allowed, encouraged, and required that clinical data be transferable electronically among organizations. The following are the ICSI data standard requirements for ICSI member organizations: the Health Level 7 (HL7) is to be used for data transmission [1]. Fields to be used include: 1) Social Security Number (SSN): The SSN was chosen as the patient identifier for the reasons listed in [2]. Record the official SSN assigned by the Social Security Administration; record a pseudo-SSN if a social security number is not available following the Veterans Administration (VA) Hospital algorithm. 2) Name: Use the American National Standards Institute (ANSI) Healthcare Informatics Standards Planning Panel (HISPP) and Message Standards Developers Subcommittee (MSDS) Standard for representation of a person's name [3]; completely record all of the person's legal name (including any punctuation, hyphenated and double last names); nicknames and appellations are to be recorded separately; salutations and suffixes are optional, but must be placed in separate computer fields from other name parts. 3) Gender: Allowable values include FEMALE, MALE, OTHER, UNKNOWN. 4) Date of Birth: Include the day, month, year (including century); permitted is approximate or estimated birth dates provided they are indicated as such. Use the ANSI HISPP MSDS standard for date representation [4]. 5) Address: Record at least one address; multiple addresses desirable identified by type or usage (i.E., home, business, office). Allow two or more lines for street, city, U.S. state or Canadian Province; identify by standard two-letter postal abbreviation--zip code (at least 5-digits, preferably 9) or postal code and country. 6) Home ID or Medical Record Number (MRN): Record if different than Social Security Number.

Female↗
PubMed1994

Preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis.

The central nervous system lesions of multiple sclerosis (MS) can be detected by magnetic resonance imaging (MRI) and the initial perivascular inflammatory component is distinguished by the presence of gadolinium enhancement. To assess the effect of systemic lymphocyte depletion on disease activity, seven patients with MS received a 10-day intravenous course of the humanised monoclonal antibody CAMPATH-1H (anti-CDw52). With some variations in the protocol, enhanced cerebral MR images were obtained monthly for 3-4 months before and at least 6 months after treatment. 28 enhancing areas were detected on the first series of 7 scans; 51 additional active lesions were identified on 18 scans before treatment; 15 were detected on 20 scans done over the next 3 months, but only 2 active lesions were seen on 23 scans during follow-up beyond 3 months. The difference in lesion incidence rate before and after treatment varied and the rate ratio was significantly reduced in only three patients. Collectively, in a "meta-analysis", the rate ratios were 0.15 [corrected] (95% CI 0.09-0.24) for all seven patients and 0.24 (0.14-0.42; p < 0.001) with exclusion of the patient whose scanning schedule differed. The effect of CAMPATH-1H on disease activity provides direct, but preliminary, evidence that disease activity in MS depends on the availability of circulating lymphocytes and can be prevented by lymphocyte depletion. It is too early to say anything about the clinical results of treatment with this agent.

Antigens, CD↗
PubMed1994

Formation of extrachromosomal circular DNA in HeLa cells by nonhomologous recombination.

Extrachromosomal circular DNA (eccDNA) generated from chromosomal DNA is found in all mammalian cells and increases with cell stress or aging. Studies of eccDNA structure and mode of formation provide insight into mechanisms of instability of the mammalian genome. Previous studies have suggested that eccDNA is generated through a process involving recombination between repetitive sequences. However, we observed that approximately one half of the small eccDNA fragments cloned from HeLa S3 cells were composed entirely of nonrepetitive or low-copy DNA sequences. We analyzed four of these fragments by polymerase chain reaction and nucleotide sequencing and found that they were complete eccDNAs. We then screened a human genomic library with the eccDNAs to isolate the complementary chromosomal sequences. Comparing the recombination junctions within the eccDNAs with the chromosomal sequences from which they were derived revealed that nonhomologous recombination was involved in their formation. One of the eccDNAs was composed of two separate sequences from different parts of the genome. These results suggest that rejoining of ends of fragmented DNA is responsible for the generation of a substantial portion of the eccDNAs found in HeLa S3 cells.

Base Sequence↗
PubMed1994

Triplex formation by the human Ha-ras promoter inhibits Sp1 binding and in vitro transcription.

The central role of the ras oncogenes in the pathogenesis of a wide variety of human malignancies is well established. Toward developing specific transcriptional inhibitors of the human Ha-ras oncogene, we have designed oligonucleotides to target a region of the Ha-ras promoter (-8 to -28) which contains two of the three Sp1 binding sites essential for transcriptional activity. Gel mobility analysis and DNase I footprinting demonstrate that an oligonucleotide (HR21ap) forms a sequence-specific triple helix with its target site in an antiparallel orientation with respect to the purine-rich duplex strand through predominantly G*G:C triplets. Within the Ha-ras promoter, HR21ap binds exclusively to the proximal target Sp1 sites over a similar nontarget distal sequence which, like the target, contains a consensus Sp1 site. Protein binding assays demonstrate that triplex formation by HR21ap inhibits Sp1 binding to the Ha-ras promoter. Moreover, oligonucleotide-directed triplex formation arrests Ha-ras promoter-dependent transcription in vitro. The results presented here suggest that triplex formation by the Ha-ras promoter targeted oligonucleotide may provide a means to specifically inhibit transcription of this oncogene in vivo.

Base Sequence↗
PubMed1994

Effect of abasic linker substitution on triplex formation, Sp1 binding, and specificity in an oligonucleotide targeted to the human Ha-ras promoter.

A region of the human Ha-ras promoter (-8 to -28) which contains two of the three Sp1 binding sites essential for transcriptional activity forms a sequence specific oligonucleotide-directed pur*pur:pyr triple helix. The relative binding of oligonucleotides containing different substitutions, including an abasic propanediol linker, over three potentially destabilizing C:G interruptions in the otherwise poly G:poly C target was examined. DNase I footprint titrations reveal that substitution of the positively charged abasic propanediol linker results in approximately ten fold greater binding than cytosine substitution which in turn provides greater sequence specific binding than substitution of a guanine in the third strand oligonucleotide over the C:G interruptions. Protein binding assays demonstrate that triplex formation by the linker substituted oligomer (HR21Xap) is less effective in inhibiting Sp1 binding than the cytosine substituted oligomer (HR21ap) both to the target sequence as well as an upstream sequence. As an indication of the effect of linker substitution and targeting consensus Sp1 sites on triplex specificity, the relative ability of the Ha-ras promoter targeted oligonucleotides to interact with non-target Sp1 sequences within the Ha-ras promoter as well as in the DHFR promoter and HIV-1 LTR was also investigated. At concentrations which afford complete DNase I protection of the target sequence, HR21ap does not bind to the non-target sequences while HR21Xap interacts weakly only at a distal site in the DHFR promoter. Also, HR21ap as well as HR21Xap are specific in their inhibition of Sp1 binding. These results suggest that the propanediol linker is able to skip over interruptions in a target sequence thereby stabilizing triplex but, slightly compromises sequence specificity and the ability to inhibit Sp1 binding to the Ha-ras promoter.

Base Composition↗
PubMed1994

Potential bacterial contamination of eyedrops used for tonometry.

We compared the potential for bacterial contamination of a proparacaine hydrochloride solution preserved with benzalkonium chloride, which is used with fluorescein paper for tonometry, to that of a fluorescein-benoxinate hydrochloride combination solution preserved with chlorobutanol. We contaminated bottles of each solution with Pseudomonas aeruginosa or Staphylococcus aureus (10(7) organisms per milliliter of eyedrop solution). From the fluorescein-benoxinate hydrochloride solution, Staphylococcus organisms were cultured in declining numbers over time, with a half-life of nine seconds, and no Staphylococcus organisms were recovered after five minutes. Pseudomonas organisms disappeared from this solution within 15 seconds. Neither species was viable after 15 seconds in the proparacaine hydrochloride solution. Additionally, we cultured 12 bottles of fluorescein-benoxinate hydrochloride and 15 bottles of proparacaine hydrochloride that had been in use in the clinic for one month. No organisms were recovered from a drop dispensed from any bottle or from the tips, caps, rims, or solution from within any bottle, except that five colonies of Staphylococcus grew from the external rim of one bottle. We conclude that both solutions sterilize themselves rapidly and effectively. Either may be used safely for tonometry.

Bacteriological Techniques↗
PubMed1994

Inhibition of nuclear protein binding to the human Ki-ras promoter by triplex-forming oligonucleotides.

The human Ki-ras promoter contains a 22 base pair homopurine.homopyrimidine (pur.pyr) motif within a region that is nuclease-hypersensitive in both native chromatin and supercoiled plasmids. Gel mobility shift analysis and competition experiments show that this pur.pyr motif binds a nuclear protein(s) in a sequence-specific manner. Several observations suggest that the nuclear protein may be an important regulatory factor. Gel mobility shift analysis and DNase I footprinting demonstrate that oligonucleotides can be targeted to this motif forming sequence-specific purine*purine.pyrimidine (pur*pur.pyr) or mixed purine/pyrimidine*purine-pyrimidine (pur/pyr*pur.pyr) intermolecular triple helices through guanine (G) recognition of guanine.cytosine (G.C) base pairs and either adenine (A) or thymine (T) recognition of adenine-thymine (A.T) base pairs in the target sequence. Triple helices containing either T*A.T or A*A.T triplets are formed exclusively with oligonucleotides antiparallel to the homopurine target strand. The affinity of an oligonucleotide which forms T*A.T triplets is approximately equal to, or slightly greater than, the affinity of an oligonucleotide which forms A*A.T triplets. Oligonucleotide-directed triplex formation inhibits sequence-specific nuclear protein binding to the K-ras promoter. These observations suggest that triplex formation by the oligonucleotides described here may provide a means to specifically inhibit transcription of the K-ras oncogene.

Base Composition↗