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Biomedical subjects

T Allen

Publications and source records attributed to T Allen.

At least 55 records · Page 3Linked to original sources

Physician directed networks: the Renaissance perspective.

It is time for all providers, physicians, hospital executives and ancillary providers to find creative ways to meet the healthcare needs of their local communities. More efficient systems of health care delivery will come from noncompetitive partnerships based on shared visions, collaborations, openess, honesty and integrity. RHP can be a catalyst for physicians and other providers in the Kansas City area and throughout the state to respond to the challenges and opportunities that lie before them.

Community Health Services↗

Computer-assisted trauma care prototype.

Each year, civilian accidental injury results in 150,000 deaths and 400,000 permanent disabilities in the United States alone. The timely creation of and access to dynamically updated trauma patient information at the point of injury is critical to improving the state of care. Such information is often non-existent, incomplete, or inaccurate, resulting in less than adequate treatment by medics and the loss of precious time by medical personnel at the hospital or battalion aid station as they attempt to reassess and treat the patient. The Trauma Care Information Management System (TCIMS) is a prototype system for facilitating information flow and patient processing decisions in the difficult circumstances of civilian and military trauma care activities. The program is jointly supported by the United States Advanced Research Projects Agency (ARPA) and a consortium of universities, medical centers, and private companies. The authors' focus has been the human-computer interface for the system. We are attempting to make TCIMS powerful in the functions it delivers to its users in the field while also making it easy to understand and operate. To develop such a usable system, an approach known as user-centered design is being followed. Medical personnel themselves are collaborating with the authors in its needs analysis, design, and evaluation. Specifically, the prototype being demonstrated was designed through observation of actual civilian trauma care episodes, military trauma care exercises onboard a hospital ship, interviews with civilian and military trauma care providers, repeated evaluation of evolving prototypes by potential users, and study of the literature on trauma care and human factors engineering. This presentation at MedInfo '95 is still another avenue for soliciting guidance from medical information system experts and users. The outcome of this process is a system that provides the functions trauma care personnel desire in a manner that can be easily and accurately used in urban, rural, and military field settings. his demonstration will focus on the user interfaces for the hand-held computer device included in TCIMS, the Field Medic Associate (FMA). The FMA prototype is a ruggedized, water-resistant personal computer, weighing approximately 5 lbs. It has an LCD graphical user interface display for patient record input and output, pen-based and audio input, audio output, and wireless communications capabilities. Automatic recording and dynamic, graphical display of time-stamped trends in patient vital signs will be simulated during the demonstration. Means for accessing existing patient record information (e.g., allergies to particular medications) and updating the record with the nature of the injury, its cause, and the treatments that were administered will be shown. These will include use of an electronic pen to mark up anatoglyphs (standard drawings of human body appearing on computer screen) to show where injuries occurred and where treatments were applied, and to input textual descriptions of the nature of the injury, its cause, what treatments were administered, etc. Computer recognition of handwritten inputs will be shown. Likewise, voice annotation and audio playback of patient record information by medics and hospital personnel will be illustrated. These latter technologies free the care providers' hands to treat the patient; they can therefore provide inputs to the patient record while information is fresh in their minds. The audio playback option allows hospital personnel to select more detailed voice annotations of specific portions of the patient record by simply touching the electronic pen to a particular place where an electronic pen marking was made by a medic in the field and then listening to the medic's corresponding audio commentary. Finally, the FMA's means for assisting the medic in simultaneously managing several injured patients will be shown. (abstract truncated)

Emergency Medical Services↗

Basic fibroblast growth factor increases the multiplication and migration of a serum-free derivative of CACO-2 but does not affect differentiation.

Basic fibroblast growth factor (bFGF) is found in the extracellular matrix and around the endothelial and epithelial cells of some human colon carcinomas. It is believed to play a role in angiogenesis, but in addition, recent data suggest that it can directly stimulate mitogenesis in some colon carcinoma cell lines. To clarify the role of bFGF in human colon carcinoma, we developed a model of Caco-2 which grew in serum-free conditions so that the effect of bFGF on multiplication, migration, and differentiation could be studied in defined conditions. Through morphological and biochemical studies in serum-free conditions, we demonstrated that this subline of Caco-2 differentiated spontaneously on reaching confluence. Using this model, we found that bFGF did not affect differentiation but that multiplication and migration were increased. The implication of these findings is that bFGF, released from the extracellular matrix by invading cells or produced by neovascular endothelial cells, can increase the mitogenic rate and migratory potential of colon carcinoma cells. In addition, the dual role of bFGF in stimulating colon carcinoma cells directly and promoting angiogenesis suggests that anti-bFGF strategies could form the basis of a novel approach to the treatment of colon carcinoma.

Cell Differentiation↗

Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly.

Split hand/split foot (ectrodactyly; SHSF) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1; the locus has been designated SHFD1. We have constructed a physical map consisting of overlapping yeast artificial chromosome clones for the entire region. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients. An SHFD1 critical interval of 1.5 Mb was established by analysis of five patients with deletions. Translocation or inversion breakpoints found in six patients were mapped within 700 kb of each other in the critical region. Of note is that eight of the patients analyzed (67%) are in fact classified as having syndromic ectrodactyly. Thus, these mapping data establish a relationship between simple split hand/split foot and this more complex group of human birth defects. Finally, we have mapped DLX5, a member of the Distal-less homeobox gene family, to the SHFD1 critical interval.

Abnormalities, Multiple↗

Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21.3-q22.1.

Split hand/split foot (SHFD) is a human developmental defect characterized by missing digits, fusion of remaining digits, and a deep median cleft in the hands and feet. Cytogenetic studies of deletions and translocations associated with this disorder have indicated that an autosomal dominant split hand/split foot locus (gene SHFD1) maps to 7q21-q22. To characterize the SHFD1 locus, somatic cell hybrid lines were constructed from cytogenetically abnormal individuals with SHFD. Molecular analysis resulted in the localization of 93 DNA markers to one of 10 intervals surrounding the SHFD1 locus. The translocation breakpoints in four SHFD patients were encompassed by the smallest region of overlap among the SHfD-associated deletions. The order of DNA markers in the SHFD1 critical region has been defined as PON-D7S812-SHFD1-D7S811-ASNS. One DNA marker, D7S811, detected altered restriction enzyme fragments in three patients with translocations when examined by pulsed-field gel electrophoresis (PFGE). These data map SHFD1, a gene that is crucial for human limb differentiation, to a small interval in the q21.3-q22.1 region of human chromosome 7.

Adult↗

Molecular characterization of phosphoribosylpyrophosphate synthetase from Leishmania donovani.

The phosphoribosylpyrophosphate synthetase (PRS) enzyme from parasitic protozoa plays a critical role in the acquisition of exogenous purine bases by providing the phosphoribosylpyrophosphate substrate for phosphoribosylation. To characterize a PRS enzyme from parasitic protozoa, the prs gene was isolated from a genomic library of Leishmania donovani DNA. A 1936-bp SalI fragment was sequenced that encompassed an open reading frame of 1113 nucleotides encoding a polypeptide of 371 amino acids and 40 787 Da. After gap alignment, the leishmanial PRS exhibited 40-42% amino acid identity with a variety of mammalian and prokaryotic PRSs. L. donovani PRS also contained an approx. 20-amino acid stretch that was highly homologous to the phosphoribosylpyrophosphate binding domains of mammalian phosphoribosyltransferase enzymes. Two prs-specific transcripts of 2.6 and 2.1 kb were detected by Northern analysis, and Southern blots of genomic DNA implied that the prs locus was not tandemly repeated in the L. donovani genome. PRS activity was detected in L. donovani extracts, and apparent Km values of approx. 30 microM and approx. 1 mM were calculated for ribose-5-phosphate and ATP, respectively. PRS was sensitive to inhibition by AMP and ADP but refractory to IMP, GMP, GTP, CTP, and UTP. The high apparent Km value of the parasite enzyme for ATP and its insensitivity to inhibition by many nucleotides suggested that kinetic differences between the L. donovani and human PRSs could provide an avenue for rational therapeutic manipulation of parasitic disease. The isolation of the L. donovani prs gene now provides an opportunity to genetically dissect the determinants responsible for the function and regulation of this indispensable enzyme of purine and pyrimidine metabolism in a genus of parasitic protozoa.

Amino Acid Sequence↗

Molecular characterization of the ldmdr1 multidrug resistance gene from Leishmania donovani.

The ldmdr1 gene that confers resistance to multiple structurally dissimilar hydrophobic drugs in Leishmania donovani has been isolated within a 5.4-kb XmaI fragment from a genomic library of L. donovani DNA and its protein coding region sequenced. The longest open reading frame within ldmdr1 encodes a 146.5-kDa protein of 1341 amino acids, designated LDMDR1. The primary structure and predicted membrane topology of LDMDR1 indicates that it is a member of the P-glycoprotein superfamily with the greatest homology to the mammalian multidrug resistance P-glycoproteins. A 2.3-kb SalI fragment derived from a second ldmdr1 allele was also cloned from the L. donovani library. Nucleotide sequence analysis of a portion of the SalI insert revealed 5 single base differences from its counterpart within the 5.4-kb XmaI fragment, one of which created a PvuI restriction site polymorphism. Southern blots of PvuI-digested DNA divulged that the amplified ldmdr1 gene copies in a multidrug-resistant L. donovani strain were all derived from the single ldmdr1 allele whose protein coding segment was sequenced in its entirety.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Localisation of granulocyte macrophage colony-stimulating factor in human long-term bone marrow cultures. Biological and immunocytochemical characterisation.

The distribution of granulocyte macrophage colony-stimulating factor (GM-CSF) in human long-term bone marrow cultures (HLTBMC) was examined using two monoclonal antibodies raised using purified recombinant GM-CSF and a third commercially available GM-CSF antibody. The antibodies were able to bind to purified recombinant GM-CSF and showed inhibition of GM-CFC colonies in the presence of both recombinant and native protein. All antibodies displayed similar patterns of distribution in both permeabilised and non-permeabilised stromal cell preparations. Fibroblasts were labelled at their periphery in early cultures and both endothelial cells and fibroblasts showed cytoplasmic labelling with anti-GM-CSF. The fact that GM-CSF appears to be sequestered by cells of the bone marrow stroma raises the possibility that it is synthesized by these cells and may regulate activity of the progenitor cells in the haemopoietic foci. In contrast, early progenitor cells within the foci did not stain with any of the anti-GM-CSF antibodies. Adipocytes, which differentiate from fibroblasts in these cultures, showed a diffuse staining pattern. Two types of macrophage staining were observed in the non-permeabilised cells; those exhibiting only autofluorescence and those that bound the antibody. Intracellular staining was apparent in a small sub-population. Generally, the staining persisted up to eight weeks of culture and thereafter declined, becoming virtually undetectable after 12 weeks. This correlates with the pattern of GM-CFC production in long-term bone marrow cultures.

Blotting, Western↗

Effects of the 5-HT1A partial agonists gepirone, ipsapirone and buspirone on local cerebral glucose utilization in the conscious rat.

The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxy-glucose autoradiography. All three 5-HT1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20-25% and increased glucose utilization by 38-65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbic-habenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone.

Animals↗

The putative 5-HT1A antagonist BMY 7378 blocks 8-OH-DPAT-induced changes in local cerebral glucose utilization in the conscious rat.

It has previously been shown that the 5-HT1A agonist, 8-OH-DPAT, caused discrete changes in cerebral glucose utilization in the rat, as assessed by quantitative 2-deoxyglucose autoradiography. Here, the effect of the putative 5-HT1A antagonist, BMY 7378, on regional cerebral glucose utilization was examined, when injected alone and in rats treated with 8-OH-DPAT. In control rats, BMY 7378 (5 mg/kg, s.c.) markedly increased glucose utilization in the lateral habenular nucleus and moderately reduced glucose utilization in the hippocampal formation. Pretreatment with BMY 7378 (5 mg/kg) significantly attenuated the reductions in glucose utilization in the hippocampus, entorhinal, piriform and cingulate cortex, induced by 8-OH-DPAT (0.25 mg/kg). The 8-OH-DPAT-induced increase in glucose utilization in the copula pyramis, that is putatively associated with the appearance of the 5-HT behavioural syndrome, was also blocked by BMY 7378, as was the behavioural syndrome. In summary, BMY 7378 produced few of the discrete changes in cerebral glucose utilization that are seen with 8-OH-DPAT. However, many of the changes induced by 8-OH-DPAT were reversed by BMY 7378. These data are consistent with the hypothesis that the effects of 8-OH-DPAT on regional cerebral glucose utilization are mediated by 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Cloning of the gene encoding Leishmania donovani S-adenosylhomocysteine hydrolase, a potential target for antiparasitic chemotherapy.

A full-length gene encoding the S-adenosylhomocysteine hydrolase (AdoHcyase) enzyme has been isolated from a genomic library of Leishmania donovani DNA in lambda GEM-11 by cross-hybridization to the full-length human AdoHcyase cDNA. The nucleotide sequence of the SalI fragment contained a single open reading frame that encoded a polypeptide of 438 amino acids (47,712 Da). After maximum gap alignment, the predicted amino acid sequence of the leishmanial AdoHcyase was 70-73% identical to AdoHCyases from higher eukaryotes. In addition, a data base search revealed that the primary structure of all AdoHcyase proteins was highly homologous to that of a protein encoded by a mRNA from Drosophila melanogaster that maps near the r element function of the Abd-b homeotic gene. In Northern blots, the SalI fragment hybridized to a 3.0-kb transcript that presumably encodes the parasite enzyme. Southern blot analysis of genomic DNA revealed that the AdoHcyase gene did not exist as a tandemly repeated array within the L. donovani genome. Moreover, monoclonal antibodies generated against human AdoHcyase recognized a leishmanial protein on immunoblots. Finally, the growth of L. donovani promastigotes could be arrested by micromolar concentrations of 3-deazaaristeromycin (C3Ari) and 9-(trans-2',trans-3'-dihydroxycyclopentanyl)adenine, 2 known inhibitors of mammalian AdoHcyase. C3Ari also induced a substantial expansion of the intracellular pools of both AdoHcy and S-adenosylmethionine (AdoMet), as well as a significant diminution of the AdoMet/AdoHcy ratio. Thus, AdoHcyase may have therapeutic potential for the selective treatment of diseases of parasitic origin.

Adenosine↗

Alterations in EEG amplitude, personality factors, and brain electrical mapping after alpha-theta brainwave training: a controlled case study of an alcoholic in recovery.

A controlled case study was conducted of effects of EEG alpha and theta brainwave training with a recovering alcoholic patient who experienced craving and fear of relapse after 18 months of abstinence. Training consisted of six sessions of thermal biofeedback to increase central nervous system (CNS) relaxation. Effects were documented with pretreatment and post-treatment personality testing, 20-channel digitized EEG evaluations both under relaxed conditions and under stress, minute-by-minute physiologic recordings of autonomic and EEG data during each training session, blood pressure, and heart rate indications taken both during relaxation and under stress, and by clinical observation. Results replicated those of a previous controlled study with chronic alcoholic patients not abstinent prior to treatment. New findings include post-treatment indications of more relaxed CNS functioning under stress, and of reduced autonomic activation both during relaxation and under stress. Brain-mapping indications of anxiety associated with painful cold-pressor stimulation were seen only in the pretest readings; at post-test the brain map indicated pain-associated EEG activity in the contralateral somatosensory area, but no apparent anxiety-associated EEG activity. At 4 months post-treatment the patient's wife and colleagues report the patient appears to function in a more relaxed way under the impact of stress, and he reports no longer experiencing craving for alcohol. Overall, support is provided for the possibility that alpha and theta brainwave training may be a useful intervention for the abstinent alcoholic experiencing stress-related craving and fear of relapse.

Adult↗

A novel structure associated with a lampbrush chromosome in the chicken, Gallus domesticus.

At a site near the end of the short arms of lampbrush bivalent 2 in the chicken (Gallus domesticus) there is always a marker structure that appears in the phase-contrast light microscope as a solid object with diffuse edges measuring about 4 microns across. When examined by transmission electron microscopy in thin section, this object appears as a loose bundle of fibres. In some preparations individual fibres appear 15-16 nm thick, smooth in outline and solid in cross-section. In other preparations they are 32-38 nm thick, rougher in outline and ring-like in cross-section. High-resolution scanning electron micrographs of the chromosome 2 marker show it to be a loose bundle of spaghetti-like fibres that is quite unlike anything previously seen on a lampbrush chromosome of any organism. As with the sectioned material, fibres in some preparations were smooth and 15-16 nm in diameter, whereas those in others were more knobbly and about 35 nm thick. The fibres appear to branch and in some cases it is clear that the daughter strands of a branch have the same dimensions as the parent strand. Free ends are rare. Total length of fibre material present at one marker locus is estimated to be between 500 and 2000 microns. Similar structures are not present on the lampbrush chromosomes of quail, wood pigeon or chaffinch. The nature of this fibrous marker, referred to in this paper as the "spaghetti marker", is discussed in relation to lampbrush chromosome function and to events that take place during the lampbrush phase of oogenesis in chicken. Evidence is discussed in relation to the possibility that the chromosome 2 marker represents a novel form of nuclear RNP or the specific association of some structural protein with one chromosome locus.

Animals↗