Older drivers and physicians.
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Biomedical subjects
Publications and source records attributed to R Martinez.
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The protein tyrosine kinase PYK2, which is highly expressed in the central nervous system, is rapidly phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration, as well as by protein kinase C activation. Activation of PYK2 leads to modulation of ion channel function and activation of the MAP kinase signalling pathway. PYK2 activation may provide a mechanism for a variety of short- and long-term calcium-dependent signalling events in the nervous system.
We are investigating the nature of the chemical interactions between the neuropeptide Y (NPY) and its cell surface receptor (Y1). A previous study involving site-directed mutagenesis and computer-aided modelling (Walker et al., 1994) suggested that the C-terminal Tyr36 of NPY, known to be a key residue for receptor binding, might dock at a pocket formed by hydrophobic amino acids of transmembrane domains (TM) 1, 2, 6 and 7 of the Y1 receptor. To investigate which residues were required for ligand binding, we mutated the sequences encoding F41, L43, F96, Y100, F286 and H298 of the human Y1 receptor. The mutant cDNAs were transiently expressed in Hela cells and the ability of the encoded proteins to bind NPY was evaluated. Replacing F41, L43 or F96 with alanines had no effect on NPY binding. On the contrary, Y100, F286 and H298 appeared to be residues critical for ligand binding. In particular, the removal of the hydroxyl group of Y100 (Tyr100-->Phe100 mutation) yielded a protein devoid of affinity for the ligand. The level of expression and the presence on the cell surface of mutants lacking NPY binding activity was assessed by immunological techniques. In addition, we tested the ability of synthetic analogues of neuropeptide Y with substitutions at position 36 to bind to the Y1 receptor. To get spatial insight into the relative positions of the above mentioned residues we constructed a molecular model of the interaction between NPY:Y36 and the elements of the hydrophobic pocket surrounding this residue.
Chronic myelogenous leukemia evolves in two clinically distinct stages: a chronic and a blast crisis phase. The molecular changes associated with chronic phase to blast crisis transition are largely unknown. We have identified a cDNA clone, DR-nm23, differentially expressed in a blast-crisis cDNA library, which has approximately 70% sequence similarity to the putative metastatic suppressor genes, nm23-H1 and nm23-H2. The deduced amino acid sequence similarity to the proteins encoded by these two latter genes is approximately 65% and includes domains and amino acid residues (the leucine zipper-like and the RGD domain, a serine and a histidine residue in the NH2- and in the COOH-terminal portion of the protein, respectively) postulated to be important for nm23 function. DR-nm23 mRNA is preferentially expressed at early stages of myeloid differentiation of highly purified CD34+ cells. Its constitutive expression in the myeloid precursor 32Dc13 cell line, which is growth-factor dependent for both proliferation and differentiation, results in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor and causes apoptotic cell death. These results are consistent with a role for DR-nm23 in normal hematopoiesis and raise the possibility that its overexpression contributes to differentiation arrest, a feature of blastic transformation in chronic myelogenous leukemia.
Receptor-type protein tyrosine phosphatase beta (RPTP beta) is expressed in the developing nervous system and contains a carbonic anhydrase (CAH) domain as well as a fibronectin type III repeat in its extracellular domain. Fusion proteins containing these domains were used to search for ligands of RPTP beta. The CAH domain bound specifically to a 140 kDa protein expressed on the surface of neuronal cells. Expression cloning in COS7 cells revealed that this protein is contactin, a GPI membrane-anchored neuronal cell recognition molecule. The CAH domain of RPTP beta induced cell adhesion and neurite growth of primary tectal neurons, and differentiation of neuroblastoma cells. These responses were blocked by antibodies against contactin, demonstrating that contactin is a neuronal receptor for RPTP beta. These experiments show that an individual domain of RPTP beta acts as a functional ligand for the neuronal receptor contactin. The interaction between contactin and RPTP beta may generate unidirectional or bidirectional signals during neural development.
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Telemedicine systems that provide health delivery services to rural clinics and hospitals are being demonstrated in clinical settings. This paper summarizes the research and consortia projects at the University of Arizona Medical Center. The paper describes the Rural and Global Picture Archiving and Communications (PACS) environment developed under a National Science Foundation grant. The Rural and Global PACS environment includes many workstations, database, and networking components and is treated as a large distributed system. These components are described in this paper. The multimedia services for radiology provided by the Rural and Global PACS are described and their performance is measured. Finally, the current research work using the Open Software Foundation's distributed computing environment (OSF DCE) services is described. An OSF DCE testbed for the Rural and Global PACS is described and the rationale of using OSF DCE in the project is presented.
Cerebral infarct (stroke) causes striatal damage with subsequent deterioration of sensorimotor and cognitive functions that may be mediated by the dopamine receptor system. In the present study, transient, focal ischemia was induced in Sprague-Dawley rats by middle cerebral artery occlusion. Ischemic animals exhibited significantly less dopamine antagonist (haloperidol)-induced catalepsy and more dopamine agonist (amphetamine)-induced hyperactivity than sham-operated animals. Younger ischemic animals showed more profound behavioral alteration but also displayed greater recovery over time than older ischemic animals. Histologic data revealed a lateral striatal lesion in all ischemic animals. These results place the striatal dopaminergic system as a possible strategic venue for the treatment of cerebral ischemia. In addition, aging is found to be a risk factor for stroke as noted in humans.
We have expressed the human Y1 NPY receptor in insect cells using a recombinant baculovirus (BacY1). Non-linear curve fitting of competition binding data indicates the presence of 500,000-750,000 saturable NPY binding sites per cell. The affinity of the recombinant Y1 receptor for NPY (Kd = 0.38 +/- 0.8 nM) was identical to the natural receptor. We used a foreign epitope to characterize, immunopurify, and localize the recombinant protein. Cross-linking experiments identified a 65 kDa band as the major NPY binding species. Confocal microscopy indicated that although some recombinant proteins are detectable as early as 12 h post-infection, significant expression at the cell surface is only seen 24-48 h post-infection. We also describe a procedure to treat infected Sf21 cells in such a way that they can be frozen and stored at -80 degrees C for many months before being used for binding studies.
OBJECTIVE: To implement and evaluate a practice model for telepathology. METHODS: A case triage practice model was devised in which general pathologists review all cases and refer them to subspecialists only when necessary. In 1993, the Arizona-International Telemedicine Network (AITN), a high-resolution static imaging telepathology diagnostic network, linking six sites to the University of Arizona in Tucson, began testing the model. Work flow through the network was analyzed, and diagnostic concordance was assessed in 150 surgical cases by comparing the diagnoses of the referring (transmitting) pathologists with diagnoses of the consulting (receiving) telepathologists as well as by comparing the referring pathologists' diagnoses with the consensus diagnoses reached by an independent review panel. Data analysis was controlled for subspecialty case type. Telepathologists had access to the referring pathologists' preliminary diagnoses, and the review panel had access to the original glass slides and the surgical pathology reports prior to rendering their respective diagnoses. RESULTS: The triage pathologist completed the telepathology consultation without the assistance of a subspecialty pathologist in 66% of the cases. The review panel examined the original glass slides from 134 cases by light microscopy. Concordance rates of the telepathologists' or review panel's diagnoses with the referring pathologists' diagnoses were not statistically different (93.1% v 83.6%, respectively; P > 0.05). CONCLUSION: The case triage model is suitable for the practice of telepathology. It significantly reduces the need for subspecialty pathologists. Static imaging telepathology is useful and reasonably efficient for rendering diagnostic opinions in the majority of referred cases. Tissue sampling limitations imposed by static imaging occasionally resulted in diagnostic errors.
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OBJECTIVE: Triage decisions must be based on accurate information with a valid understanding of injury patterns and their sources. Only a data base that includes both medical and collision factors can best provide the breadth of information required to achieve this goal. In the study reported here we assessed the accuracy of automobile collision data collected by emergency physicians compared with Police Accident Reports. DESIGN: Prospective study in which emergency medicine attending physicians completed questionnaires placed near the entrance to the trauma rooms in the emergency department. MATERIALS AND METHODS: During a two-month period the emergency medicine attending physicians obtained data concerning vehicle collision factors for all automobile collisions resulting in major trauma to patients over 18 years of age who were triaged to the Emergency Department at Stanford University Hospital, a level-I trauma center. These data were then compared by one of the investigators with the data contained in Police Accident Reports, which were available for 50 of the 64 patients who met the study eligibility criteria. MEASUREMENTS AND MAIN RESULTS: For each automobile collision, the attending physician was asked to collect the following data: direction of impact; extrication required; ejection; type and use of restraints; deployment of an airbag; type of vehicle; reported severity (minor, moderate, or major) of impact; presence and degree of steering wheel deformation; presence and degree of intrusion into occupant compartment; estimated speed and collision type (i.e., vehicle to vehicle, to fixed object, etc.) Nearly three-fourths (74%) of all cases had at least one discrepancy when compared with the Police Accident Reports, while 46% of these had multiple discrepancies. CONCLUSIONS: When data obtained by emergency physicians are compared with the information in Police Accident Reports, there are notable differences on several collision factors. Triage decisions must be based on accurate information with a valid understanding of injury patterns and their sources. Only a data base that includes both medical and collision factors can best provide the breadth of information required to achieve this goal.
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From car crashes to pedestrians struck to bicyclists run down, vehicle accidents are among the most common EMS emergencies. The new man in charge of overseeing the safety of the nation's highways and motor vehicles is Ricardo Martinez, MD.
Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and mortality in lung transplant patients and requires timely and accurate diagnosis. This study compares the diagnostic utility of the evaluation of transbronchial biopsy by histology, immunohistochemistry, and simultaneous culture of bronchoalveolar lavage in a population of 13 lung transplant patients who underwent 78 biopsies during a period of 27 months. Our study concludes that, in patients clinically symptomatic for CMV pneumonitis, histology alone is diagnostic for the presence of the virus, whereas culture of bronchoalveolar lavage fluid is not as helpful. In asymptomatic patients, however, immunohistochemistry utilizing monoclonal antibodies to immediate-early and early CMV nuclear antigens may indicate development of CMV pneumonitis before cytopathic changes are evident.
The Arizona-International Telemedicine Network (AITN) links 4 cities in Arizona and two international sites in China and Mexico, into a telepathology diagnostic network. Established in 1993, the Network provides second opinions on surgical pathology and cytopathology cases. Workstations are 486 PC-based computers. Static images (1024 x 774 x 8 pixels) are grabbed with a variable resolution video camera and sent by 14,400 bit per second modems over ordinary telephone lines. Second opinions are either rendered directly by a general telepathologist or triaged to a specialist. Experience with the first 37 cases indicates a high level of success in providing useful information to referring pathologists over the Network.
A case of Erdheim-Chester disease demonstrates cerebral hemispheric involvement, as well as and intraaxial and extraaxial brain stem involvement in a patient with symptoms of paraparesis, urinary incontinence, visual loss, ataxia, vertigo, proptosis, and nystagmus. Persistent gadopentetate dimeglumine enhancement was noted in the extraaxial cervicomedullary brain stem lesion 23 days after injection. However, the supratentorial lesions fail to show similar persistent enhancement. This case also demonstrates MR features characteristic of retrobulbar infiltration.