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Biomedical subjects

M Graves

Publications and source records attributed to M Graves.

At least 19 recordsLinked to original sources
PubMed1998

Driving avoidance and functional impairment in older drivers.

The purpose of this study was to examine the association between visual and cognitive impairment in older drivers and their avoidance of potentially challenging, driving situation. A group of 257 older drivers participated in assessments of visual sensory function, eye health and cognitive function including the useful field of view test, and completed a structured questionnaire on driving exposure and how frequently they avoided challenging driving situations. Results replicated earlier studies showing that many older drivers limit their exposure to driving situations which are generally believed to be more difficult (e.g. rain, night, heavy traffic, rush hour). Furthermore, older drivers with objectively determined visual and/or attentional impairments reported more avoidance than those free of impairments; those with the most impairment reported avoiding more types of situations than other less impaired or non-impaired drivers. Older drivers with a history of at-fault crashes in the prior five years reported more avoidance than those who had crash-free records. Future research should evaluate the potentially beneficial role of self-regulation in enhancing older driver safety, particularly in those older drivers with visual and attentional processing impairments who have elevated crash risk.

Aged↗
PubMed1997

HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry.

BACKGROUND: As of May 1, 1995, the National Marrow Donor Program had a donor registry consisting of over 1.35 million HLA-typed volunteers recruited from most major cities and states in the United States. This registry represents the largest single HLA-typed pool of normal individuals in the world. METHODS: We analyzed the HLA-A, -B, -DR locus phenotypes of the National Marrow Donor Program donors in order to estimate gene and haplotype frequencies for major racial groups of the United States: Caucasian American, Asian American, African American, Latin American, and Native American. The large size of the database allowed us to calculate the frequencies of relatively rare antigens and haplotypes with more accuracy than previous studies. RESULTS: We observed 89,522 distinguishable HLA-A, -B phenotypes in 1,351,260 HLA-A, -B-typed donors and 302,867 distinguishable HLA-A, -B, -DR phenotypes in 406,503 HLA-A, -B, -DR-typed donors. Gene and haplotype frequencies differed remarkably among the five racial groups, with African Americans and Asian Americans having a large number of haplotypes that were specific to their racial groups, whereas Caucasian Americans, Latin Americans, and Native Americans shared a number of common haplotypes. CONCLUSIONS: These data represent an important resource for investigators in the fields of transplantation and population genetics. The gene and haplotype frequencies can be used to aid clinicians in advising patients about the probability of finding a match within a specific ethnic group, or to determine donor recruitment goals and strategies. The information is also a valuable resource for individuals who are interested in population genetics, selection and evolution of polymorphic human genes, and HLA-disease association.

Chi-Square Distribution↗
PubMed1997

Data note system for capturing laboratory data.

The complexity of genome data limits the usefulness of traditional database management systems. The highly interconnected structure of genome data can be captured in a data representation language based on the mathematical formalism of graphs. We have tailored graphs for describing genome data and have developed a database management system, called the Data Note System, for developing small databases to capture data from genome laboratories. To simplify the use of the Data Note System, a series of tools with graphical user interfaces has been developed. The system is designed to be easy to install and use by novice database developers with a minimal amount of computer expertise. We describe the tools and present examples of their use. The system consists of a storage facility, a schema editing tool to simplify the design of small databases, and three tools for data entry and querying.

Computers↗
PubMed1997

Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation.

BACKGROUND: Many studies have separately reported abnormalities of frontal and temporal lobe structures in schizophrenia, but little is known of structural fronto-temporal associations in this condition. We investigated whether male patients with chronic schizophrenia would show abnormal patterns of correlation between regional brain volumes. METHODS: Structural magnetic resonance images of the brain in 42 patients were compared with 43 matched unaffected controls. We explored the pattern of association between regional brain volumes by correlational analyses, and non-parametrically tested for significance of between-group differences by randomization. RESULTS: The schizophrenics demonstrated significant volume deficits in several brain regions (left temporal lobe and hippocampus, right dorsolateral prefrontal cortex), and significant volume increases in the ventricular system (third ventricle and left temporal horn of the lateral ventricle). Controls demonstrated large positive correlations (r > 0.4) between prefrontal and temporal lobe regions. By contrast, inter-regional correlations significantly reduced in schizophrenics included those between prefrontal, anterior cingulate and temporal regions, and between posterior cingulate and hippocampus (P < 0.05). The most salient abnormality in patients was a dissociation between prefrontal and superior temporal gyrus volumes (P < 0.01). CONCLUSIONS: These results support the existence of a relative 'fronto-temporal dissociation' in schizophrenia which we suggest may be due to lack of mutually trophic influences during frontal and temporal lobe development.

Chronic Disease↗
PubMed1997

Four additional cases of Burkholderia gladioli infection with microbiological correlates and review.

Burkholderia gladioli has only recently been reported to be a human pathogen. Four cases of B. gladioli infection (including bacteremia, pneumonia, and cervical adenitis) in two adults and two young children are reported. Three of these four patients were severely immunocompromised. Commercial systems were frequently unable to identify this bacterium correctly. Antimicrobial susceptibility patterns indicated that B. gladioli strains were susceptible to the quinolones, aminoglycosides, and imipenem. In vitro laboratory investigations demonstrated that B. gladioli strains were susceptible to complement-mediated lysis of pooled human serum, thus implying that healthy individuals should be immune to infection. These four cases together with three previously reported cases suggest that B. gladioli primarily causes disease in severely immunocompromised individuals. The lack of mortality associated with infection, coupled with susceptibility to serum and lack of recognizable virulence-associated factors, suggests that this species has a low pathogenic potential.

Adult↗
PubMed1996

A graph conceptual model for developing Human Genome Center databases.

We have developed a representation of genome data which has proven itself useful for describing data at a Human Genome Center. Genomic data have a graph-like structure and representing the concepts and relationships of genetics as a graph simplifies the development of databases for genome laboratories. Graphs are a comfortable communication medium for biologists and computer scientists and graph diagrams assist in the development of databases by facilitating the exchange of expertise. We have tailored a graph language for modeling genomic data and describe our process of using graphs to develop genome databases.

Computer Graphics↗
PubMed1996

Regulation of HIV-1 infection in astrocytes: expression of Nef, TNF-alpha and IL-6 is enhanced in coculture of astrocytes with macrophages.

'Restricted' human immunodeficiency virus type (HIV-1) infection of astrocytes is recognized in vivo in some pediatric and adult AIDS brains and in vitro in a small proportion of transfected primary fetal astrocytes. We investigated the extent of HIV-1JR-FL expression in fetal astrocytes and macrophages cultivated alone or together. Peak HIV-1 p24 antigen titres in supernatant fluids of macrophage cultures were increased with monocyte/macrophages from certain donors and were higher when macrophages were cocultivated with astrocytes. Structural HIV-1 gene (gp 41 and pol) products (protein and mRNA) were observed only in macrophages. Ten days after HIV-1JR-FL infection, astrocytes in a monoculture were stained negative or only weakly positive (1-2+) for Nef, whereas in a coculture up to 100% of astrocytes displayed Nef staining (up to 4+) in the cytoplasm. The streptavidine-biotine-peroxidase technique with certain monoclonal antibodies to Nef (Ovod et al, 1992) was specific for infected astrocytes. The intensity of Nef staining was higher in astrocytes cultivated with monocyte/macrophages from certain donors. In the coculture, tumor necrosis factor-alpha (TNF-alpha) was expressed in the astrocyte cytoplasm earlier after coinfection with HIV-1 and cytomegalovirus (CMV) compared to infection with HIV-1 alone. Interleukin-6 (IL-6) was secreted spontaneously and transiently in uninfected cocultures, but in a prolonged fashion following HIV-1 and HIV-1/CMV infections. The interactions between HIV-1- and CMV-infected macrophages and astrocytes lead to upregulation of TNF-alpha and IL-6 and enhancement of productive HIV-1 infection of macrophages and of 'restricted' HIV-1 infection of astrocytes with implications for the pathogenesis of AIDS dementia.

Astrocytes↗
PubMed1996

Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study.

Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for < or = 56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients (66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2',5' -oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.

Adult↗
PubMed1996

Computer program to predict likelihood of finding and HLA-matched donor: methodology, validation, and application.

Approximately 65% of the patients requiring bone marrow transplantation do not have an HLA-A, -B, -DR identical sibling and therefore need to find a phenotypically matched unrelated donor. As of June 30, 1996, the National Marrow Donor Program maintains a registry of 2.31 million volunteer donors, 35% of whom are fully typed for HLA-A, -B, -DR loci. Because a majority of the donors has not been DR typed, a patient who does not find a complete match at the time of the preliminary search may elect to prospectively DR type A, B matched and A, B one-antigen mismatched donors. An efficient strategy is therefore needed for determining the likelihood that an appropriate donor exists and for deciding which of the donors that have not yet been DR typed should be tested for DR matching with the candidate. We developed a mathematical algorithm and computer program to facilitate the search for a suitable donor by donor race and phenotype. The program provides information on the likelihood of 1) finding at least one HLA-A, -B, -DR phenotypically matched donor, 2) the likelihood of finding at least one DR match among m A, B matched donors who have not yet been DR typed, and 3) the likelihood of an A, B one antigen mismatched donor of a specific phenotype being a DR match with the patient. The mathematical models underlying the program are based on basic population genetics theory and utilize HLA-A, -B, DR haplotype frequencies derived from the NMDP registry. The results of the validation study show that the prediction is highly accurate at the level of broad antigens. The algorithm and program have the potential to assist patients and physicians in optimizing their decisions regarding clinical management and resource allocation on the process of searching for a suitable unrelated bone marrow donor.

Blood Donors↗
PubMed1995

Magnetic resonance imaging volumetric measurements of the superior temporal gyrus, hippocampus, parahippocampal gyrus, frontal and temporal lobes in late paraphrenia.

Quantified magnetic resonance measurements were made of superior temporal gyrus, parahippocampal gyrus, hippocampal, frontal and temporal lobe volumes and of the planar area of the thalamus and basal ganglia structures in 47 late paraphrenic patients and 33 healthy elderly controls. The late paraphrenics were divided into 31 schizophrenics and 16 patients with delusional disorder according to ICD-10 guidelines. Patients with delusional disorder tended to have smaller left temporal volumes compared with control subjects and patients with schizophrenia, but this difference failed to reach accepted levels of statistical significance after correction for the effects of multiple statistical comparisons, age and total brain size. Physiological right-left asymmetry, reported for temporal and frontal lobe volumes, was present in control, schizophrenic and delusional disorder subjects but delusional disorder patients had a significantly greater degree of temporal lobe asymmetry. The results add to the evidence for heterogeneity among late-onset psychoses and emphasize the subtle nature of any structural brain abnormalities in these patients.

Aged↗
PubMed1995

Viewing genome data as objects for application development.

Genomics is becoming a data-intensive science, and an increasing number of laboratories are generating data which swamps storage in traditional paper-and-ink notebooks. Capturing the data flow requires large systems with multiple applications manipulating the same or similar data. Large systems often have conflicting requirements for data representation. Consistency across applications is a prime consideration, and appropriate data representation is an important issue in developing practical systems for molecular biologists. Graphs are a natural representation for describing genome data, while objects are good for modeling the behavior necessary for laboratory applications. We present a method for translating graph descriptions of genome data into objects using objects as views on graphs. Graph representations describe genome concepts while objects capture individual views for application development insuring consistency across genome applications.

Chromosome Mapping↗
PubMed1994

Quantitative magnetic resonance imaging volumetry distinguishes delusional disorder from late-onset schizophrenia.

BACKGROUND: Late paraphrenia is recognised as a heterogeneous disorder. This is reflected by the division of such patients into schizophrenia and delusional disorder in ICD-10. Earlier imaging studies have suggested that major structural abnormalities may be associated with the onset of psychosis in later life. METHOD: Fifty late paraphrenics and 35 age-matched healthy controls underwent structural magnetic resonance imaging of the whole brain in the coronal plane. Measurements were made of intracranial and brain volumes and the volumes of the intracerebral and extracerebral cerebrospinal fluid spaces. RESULTS: No differences in intracranial, brain or extracerebral cerebrospinal fluid volumes between patients and controls were found. Late paraphrenic patients had greater lateral and third ventricle volumes than controls and the left lateral ventricle was larger than the right. When the patients were divided into appropriate ICD-10 diagnoses: paranoid schizophrenia (n = 31) and delusional disorder (n = 16), lateral ventricle volumes in the delusional disorder patients were much greater than those of the schizophrenics and almost twice those of controls. CONCLUSIONS: Structural brain differences underly diagnostic heterogeneity within late paraphrenia. The brains of late onset schizophrenics are only subtly different from those of healthy elderly individuals.

Age of Onset↗
PubMed1993

Integrating order and distance relationships from heterogeneous maps.

There is no automatic mechanism to integrate information between heterogeneous genome maps. Currently, integration is a difficult, manual process. We have developed a process for knowledge base design, and we use this to integrate order and distance relationships between genetic linkage, radiation hybrid, and physical maps. Until now, the only way to develop a persistent, knowledge-intensive application was to either develop a new knowledge base from scratch or coerce the application to fit an existing knowledge base. This was not from lack of interest by the knowledge base or database community, but merely from a lack of theoretical tools powerful enough to tackle the problem. We import formalisms from knowledge representation, natural language semantics, programming language research, and databases. These form a strong, theoretical foundation for knowledge base design upon which we have implemented the knowledge base design tool called WEAVE.

Artificial Intelligence↗
PubMed1990

Transcription and sequence studies of a 4.3-kbp fragment from a ds-DNA eukaryotic algal virus.

A 4.3-kbp portion of the genome from the Chlorella virus, PBCV-1, has been cloned and sequenced. Minimally, five open reading frames (ORFs) were identified on this fragment. Transcriptional analysis indicates that each ORF encodes complex patterns of RNA. The total length of transcribed RNA exceeds that of the ORF indicating either post-transcriptional modification or multiple transcriptional start/stop sites. The sequence TTTTTNT, previously described as the transcriptional stop site for the early genes of vaccinia virus, is also found downstream of each of our ORFs. The regions 5' to each ORF were very A + T-rich (approx 80%) but distinct promoter sequences were not unambiguously identified.

Base Sequence↗
PubMed1989

Thymectomy for myasthenia gravis: recent observations and comparisons with past experience.

To our previous report on the results of thymectomy for myasthenia gravis in 249 patients operated on between 1954 and 1981, we add a current review of 84 patients treated between 1982 and 1987. All patients underwent a median sternotomy, although this was performed after a bilateral submammary skin incision in most of the 57 female patients. There were no operative deaths, but one late death occurred at 5 months. During a mean followup of 3.6 years, 67 patients (80%) benefited from operation with remission achieved in 30 (36%) and improvement noted in 37 (44%). Acetylcholine receptor site antibody was present in 43 patients, of whom 19 (44%) achieved remission in contrast to 9 (27%) of the 33 patients without antibody. Hyperplasia of the excised thymus in 38 patients was associated with remission in 20 (53%) in contrast to remission in 7 (20%) of the 35 patients whose glands were "normal" or atrophic. The best prognosis was found in the 23 patients who had both receptor site antibody and thymic hyperplasia, as remission occurred in 15 of them (65%) in contrast to only 6 (27%) of the 22 patients who had neither factor. Remission rates (remissions per 1,000 patient-months of follow-up) for the present series (84 patients), the previous group (249 patients), and the overall group (333 patients) are 9.95, 6.13, and 6.62, respectively.

Adult↗