Search PubMed⌕ Search

Biomedical subjects

R A Miller

Publications and source records attributed to R A Miller.

At least 235 records · Page 13Linked to original sources
PubMed1992

Does too much urology damage your eyesight? Study of macular function.

A study comparing the macular function of both eyes of 130 urological surgeons was carried out to investigate whether the increased light exposure to the endoscoping eye caused any deterioration of macular function. The non-endoscoping eye was used as a control. A sophisticated computer test of colour contrast sensitivity was used. The computer assesses the degree of brightness at which the subject is just able to detect a coloured grating, and for each eye this is expressed as a threshold for the red/green axis and the blue/yellow (tritan) axis. The subjects also completed a questionnaire about their working patterns and their general and ophthalmic history and had a brief examination of the fundus. The results do not suggest that urologists are suffering any significant macular damage as a result of their work with endoscopes.

Color Perception↗
PubMed1992

Blue light emission from urological equipment. Can it damage the eyes?

Blue light present in the visible spectrum at the lower wavelengths can cause damage to the retinas of monkeys and rats. In the present study the light sources and instrumentation available to the urologist were evaluated to see whether they posed a hazard. The light emitting directly from the sources, cables and telescopes was tested and these levels were found to be dangerous to the eye when compared with the safety limit recommended by the American Conference of Governmental Industrial Hygienists (ACGIH). When the light at the eyepiece of the telescopes which had been reflected off a surface was measured, the blue light levels did not appear to be harmful when compared with the ACGIH safety limit. The use of filters is discussed and the transmission of 2 types of filters shown. While the level of blue light emission from the eyepiece remains within the ACGIH level, there are no data on long-term exposure. The addition of a blue light filter may be beneficial until such time as videoendoscopy becomes the norm. The light from light sources should be protected by a shutter and more care taken with the emission from cables and telescopes.

Equipment Safety↗
PubMed1992

CHARTLINE: providing bibliographic references relevant to patient charts using the UMLS Metathesaurus Knowledge Sources.

A successful medical informatics program helps its users to match their information needs as closely and efficiently as possible to the capabilities of the system. CHARTLINE is a computer program whose input is a free text, "natural language" patient chart in ASCII format. Using the UMLS Metathesaurus Knowledge Sources, CHARTLINE can suggest bibliographic references relevant to the patient case described in the chart. The program does not attempt to "understand" the natural language content of the chart. CHARTLINE only recognizes UMLS Metathesaurus Main Concept terms (or their synonyms) as they occur in the medical text, since those terms represent the tokens used to index the literature. The program depends on user feedback to determine which topics of a large number of potentially relevant subjects are of interest to the user.

Diagnosis, Computer-Assisted↗
PubMed1992

Lower spinal mobility and external immobilization in the normal and pathologic condition.

The study presented here used lateral flexion and extension roentgenograms to determine lumbosacral motion in healthy persons and in patients with spondylolisthesis. The lumbosacral corset, Jewett extension brace, and plastic thoracolumbosacral orthosis (TLSO) were then placed and repeat roentgenograms were done to see if effective immobilization could be obtained. Although individual variation existed, there appeared to be no significant difference in lower lumbar motion between the two groups studied, and the orthotics acted in a similar fashion on both the volunteers and the patients. The lumbosacral corset was unable to immobilize the L3-S1 levels. There was a statistically significant decrease in the average lateral disk space motion at L3-4 and L4-5 with the use of the Jewett brace and the TLSO (P less than .01); however, the motion was never completely eliminated. No brace could adequately immobilize the L5-S1 level, and some people demonstrated increased motion at this level while wearing the orthotics.

Adolescent↗
PubMed1991

Gerontology as oncology. Research on aging as the key to the understanding of cancer.

It is widely appreciated that age is a powerful risk factor for cancer. This review considers two possible explanations for the exponential increase in most neoplasms in the elderly, arguing in favor of the idea that tumor progression proceeds at faster rates in older mice and older persons than in younger mice and younger persons. Three processes that alter the rate of aging, i.e., speciation, food restriction, and selective breeding, have parallel effects on cancer incidence. This suggests that the two processes are intimately connected. Elucidation of the mechanism(s) by which the aging process controls the rate of tumor development deserves high priority in experimental oncology. One such possible mechanism, the age-associated decline in immunologic defenses, is discussed at length in an attempt to rehabilitate the idea that a loss of immune function may contribute to the vulnerability of the elderly to cancer.

Aging↗
PubMed1991

Structure-function relationship of lapemis toxin: a synthetic approach.

The synthetic approach to the structure-function relationship of lapemis toxin has been very useful in clarifying the important binding regions. To identify the neurotoxic binding domain(s) of lapemis toxin, several peptides were synthesized using the 9-fluorenylmethoxycarbonyl protocols. These peptides were based on the sequence of lapemis toxin, a 60-amino-acid, short-chain postsynaptic neurotoxin found in sea snake (Lapemis hardwickii) venom. The peptides were purified using high-performance liquid chromatography and sequenced to verify the correct synthesis, isolation, and purity. The synthetic peptide names and single letter sequences were Peptide A1 (15 mer) CCNQQSSQPKTTTNC Peptide B1 (18 mer) CYKKTWSDHRGTRIERGC Peptide B2 (16 mer) YKKTWSDHRGTRIERG Peptide C1 (12 mer) CPQVKPGIKLEC Peptide NS (20 mer) EACDFGHIKLMNPQRSTVWY. The peptide NS (nonsense peptide) sequence was arbitrarily determined and used as a control peptide. Biological activities of the synthetic peptides were determined by in vivo as well as by in vitro assay methods. For the in vivo assay, lethality was determined by intravenous injection in mice (Swiss Webster). For the in vitro assay, peptide binding to the Torpedo californica nicotinic acetylcholine receptor was determined. The peptides were found to be nontoxic at approximately 114 times the known LD50 of lapemis toxin. Binding studies with 125I-radiolabeled lapemis toxin and tyrosine-containing peptides indicated that lapemis toxin and peptide B1 bound the receptor, while the other peptides had no detectable binding. The central loop domain of lapemis toxin (peptide B1) plays a dominate role in the toxin's binding ability to the receptor. These results and the hydrophilicity analysis predict peptide B1 may serve as an antagonist or antigen to neutralize the neurotoxin effects in vivo.

Amino Acid Sequence↗
PubMed1991

Effects of farnesylcysteine analogs on protein carboxyl methylation and signal transduction.

Several proteins associated with signal transduction in eukaryotes are carboxyl methylated at COOH-terminal S-farnesylcysteine residues. These include members of the Ras superfamily and gamma-subunits of heterotrimeric G-proteins. The enzymes that catalyze the carboxyl methylation reaction also methylate small molecules such as N-acetyl-S-trans, trans-farnesyl-L-cysteine (AFC). AFC inhibits carboxyl methylation of p21ras and related proteins both in vitro and in vivo. Saturating concentrations of AFC cause a greater than 80% inhibition of chemotactic responses of mouse peritoneal macrophages. Our results suggest that carboxyl methylation may play a role in the regulation of receptor-mediated signal transduction processes in eukaryotic cells.

Alkyl and Aryl Transferases↗
PubMed1991

Differential sensitivity of virgin and memory T lymphocytes to calcium ionophores suggests a buoyant density separation method and a model for memory cell hyporesponsiveness to Con A.

Previous work from this laboratory has indicated that murine memory T cells differ from virgin T cells in that the former are more resistant to agents that alter intracellular [Ca]i. We have used this difference to devise a method for separating virgin from memory T cells by centrifugation over an ionomycin-containing Percoll step gradient after brief exposure to 2 microM ionomycin. Under these conditions, those T cells that are most sensitive to ionomycin-induced changes in [Ca]i become more dense and therefore travel further into the Percoll/ionomycin gradient than cells that are more resistant to ionomycin. We show that the ionomycin-resistant cell population is enriched for cells that express high levels of Pgp-1 (CD44), and low levels of CD45RB, and thus appears to consist largely of memory T cells. Both CD4 and CD8 cells can be divided into Pgp-1hi and Pgp-1lo subsets in this way. Cells recovered from such a gradient and washed to remove the ionomycin appear normally functional, i.e., neither more nor less responsive to mitogens and costimuli than untreated cells. Limiting dilution methods show that the ionomycin-sensitive (virgin) subset contains most of the Con A-responsive precursors for cytotoxicity, and most of the cells able to produce IL-2 in responses to Con A or staphylococcal enterotoxin B. Ag-specific helper memory cells are, however, found predominantly in the ionomycin-resistant fraction of the spleen and draining lymph nodes of mice infected with Schistosoma mansoni. Changes in resistance to calcium signal development may represent a fundamental distinction between virgin and memory T cells, and could contribute to differences in activation requirements between these two cell subsets.

Animals↗
PubMed1991

Ig VH gene expression among human follicular lymphomas.

Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire.

Base Sequence↗
PubMed1991

Autoantibody activity of immunoglobulins isolated from B-cell follicular lymphomas.

Previous work with monoclonal Igs (MIgs) has demonstrated that a high proportion of paraproteins bind to self-antigens such as the Fc fragment of IgG, Ii blood group antigens, cytoskeleton proteins, DNA, and myelin-associated glycoprotein (MAG). Recent work in CLL indicates that CD5+ B lymphocytes are frequently committed to production of autoantibodies. We have examined the antibody specificity of MIgs derived from the tumor cells of 31 different patients with CD5- B-cell lymphomas. Our results indicate that the tumor cells from 8 of these 31 patients (25.8%) express Igs with autoantibody activity. In two cases antibody activity was multispecific. In four cases, antibody activity was exclusively directed against the Fc fragment of IgG, whereas the two other cases bound to both Fc fragment of IgG and nuclear antigens. Most non-Hodgkin's lymphomas (NHL) are derived from CD5- B cells. These results indicate that like CLL, NHL also express Igs that frequently have autoantibody activity.

Antibodies, Monoclonal↗
PubMed1991

Analysis of protein phosphorylation patterns reveals unanticipated complexity in T lymphocyte activation pathways.

Protein kinases are considered likely to play important roles in the still dimly understood process by which mitogens induce resting T lymphocytes to enter the cell cycle. Using two-dimensional electrophoretic analysis of lysates from orthophosphate-labeled cells, we have compared patterns of phosphorylation in freshly isolated murine splenic T cells exposed to three mitogenic agents: antibody to the epsilon-chain of the TCR CD3 complex, the plant lectin Con A, and a mixture of PMA and ionomycin, which together bypass the signal transduction apparatus to activate intracellular pathways. Of 14 phosphoproteins found whose level of phosphorylation was increased (at least fivefold) by anti-CD3 epsilon antibody, 13 also responded to the mixture of PMA and ionomycin. Surprisingly, however, only 5 of these 14 also responded strongly to Con A exposure. We also identified two substrates that were phosphorylated in response to Con A but not to anti-CD3. Phosphorylation patterns were also studied in T cells exposed to either PMA or ionomycin alone, to gain further insight into the role of protein kinase C and calcium-dependent events in the activation process. Of 16 phosphoproteins that responded to mixtures of PMA and ionomycin, 4 were shown to require the ionomycin signal, 2 to require the PMA signal, and 3 others to respond only when both activators were present; the other 7 responded to either agonist added alone. In addition, we found two PMA-sensitive phosphoproteins in which phosphorylation was inhibited by ionomycin induced calcium signals. Finally, we identified several phosphoproteins which show differential responsiveness in CD4+ and CD8+ T cells. Classification of kinase substrates based on their differential susceptibility to these stimuli should provide new insights into the mode of action of agents and diseases that affect T cell activation.

Adenosine Triphosphate↗
PubMed1991

Expression of shared idiotypes in chronic lymphocytic leukemia and small lymphocytic lymphoma.

The expression of shared idiotypes (Slds) has been studied on malignant CD5+B cells from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) using a panel of 37 murine monoclonal antibodies previously demonstrated to be reactive with Slds derived from follicular B-cell lymphomas. Thirteen anti-Slds identified tumor cells from 31 of 105 (30%) CLL patients and 4 of 6 SLL patients. In comparison, the same panel of anti-Slds is reactive with 33% of follicular and diffuse B-cell lymphomas. Ten of these anti-Slds reacted with CLL cases at similar frequencies to that of the B-cell lymphomas. Two anti-Slds, which are known to react with autoantibodies, were significantly more prevalent in CLL than in B-cell lymphomas. These data confirm the presence of Slds in CLL and provide further evidence of an association between CLL and autoimmunity. The identification of a panel of antibodies reactive with a significant number of CLL and SLL patients will facilitate the application of anti-idiotype antibody therapy in these diseases.

Adult↗
PubMed1991

Clonal analysis of T-cell deficiencies in autotransplant recipients.

We have used limiting dilution culture methods to determine the frequency of mitogen-responsive T cells in peripheral blood of patients after bone marrow autotransplantation, and have compared their responsiveness to that of allotransplant recipients and normal controls. Autotransplant patients were found to have low responder cell frequencies in tests for lymphokine-secreting helper function, and for IL-2 dependent proliferator and cytotoxic function. Multiple regression analysis showed that function was lower in autotransplant patients than in allorecipients, and lower in male patients for all three functional assays. Patients with clinically significant infection tended to have lower proliferative function in both transplant groups and lower cytotoxic function in the allotransplant population. Graft-versus-host disease was associated with lower T-cell function, but was present only in the allotransplant group; therefore, it cannot account for the even lower levels of function observed in the autotransplant population. Because we observe deficits in T-cell regeneration in autotransplant recipients that are even more severe than in allorecipients, we postulate that cellular immunodeficiency after bone marrow transplantation may reflect limitations in thymic-dependent repopulation rather than an effect of genetic disparity between host and donor (eg, clinical or subclinical graft-versus-host).

Adult↗
PubMed1991

Physicians' information needs: analysis of questions posed during clinical teaching.

OBJECTIVE: To describe information requests expressed during clinical teaching. SETTING: Residents' work rounds, attending rounds, morning report, and interns' clinic in a university-based general medicine service. SUBJECTS: Attending physicians, medical house staff, and medical students in a general medicine training program. METHODS: An anthropologist observed communication among study subjects and recorded in field notes expressions of a need for information. We developed a coding scheme for describing information requests and applied the coding scheme to the data recorded. Based on assigned codes, we created a subset of strictly clinical requests. MEASUREMENTS: Five hundred nineteen information requests recorded during 17 hours of observed clinical activity were selected for detailed analysis. These requests related to the care of approximately 90 patients by 24 physicians and medical students. Sixty-five requests were excluded because they were not strictly clinical, leaving a subset of 454 clinical questions for analysis. MAIN RESULTS: On average, five clinical questions were raised for each patient discussed. Three hundred thirty-seven requests (74%) concerned patient care. Of these 337 questions, 175 (52%) requested a fact that could have been found in a medical record. Seventy-seven (23%) of these questions, motivated by the needs of patient care, were potentially answerable by a library, a textbook, a journal, or MEDLINE. Eighty-eight (26%) of the questions asked for patient care required synthesis of patient information and medical knowledge. CONCLUSIONS: Clinicians in the study settings requested information frequently. Many of these information needs required the synthesis of patient information and medical knowledge and thus were potentially difficult to satisfy. A typology is proposed that characterizes information needs as consciously recognized, unrecognized, and currently satisfied.

Education, Medical↗
PubMed1991

An interlingua for electronic interchange of medical information: using frames to map between clinical vocabularies.

The proliferation of medical knowledge has led to the development of extensive dictionaries for electronically accessing information resources. The task of standardizing terminology used for electronic hospital records and for knowledge bases for medical expert systems and indexing the medical literature cannot easily be met by developing a single, monolithic "official" medical vocabulary. Developing a monolithic vocabulary would require a massive effort, and its existence would not guarantee its use by third-party payors, by practicing clinicians, or by developers of electronic medical information systems. Recognizing this, the National Library of Medicine (NLM) has begun to develop the Unified Medical Language System (UMLS) as a means of promoting electronic information exchange among systems with controlled vocabularies. The authors describe a frame-based system developed as an experimental approach to mapping between controlled clinical vocabularies.

Cluster Analysis↗