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Biomedical subjects

M A Osborne

Publications and source records attributed to M A Osborne.

12 recordsLinked to original sources

The inositol 5'-phosphatase SHIP binds to immunoreceptor signaling motifs and responds to high affinity IgE receptor aggregation.

Immunoreceptors such as the high affinity IgE receptor, FcepsilonRI, and T-cell receptor-associated proteins share a common motif, the immunoreceptor tyrosine-based activation motif (ITAM). We used the yeast tribrid system to identify downstream effectors of the phosphorylated FcepsilonRI ITAM-containing subunits beta and gamma. One novel cDNA was isolated that encodes a protein that is phosphorylated on tyrosine, contains a Src-homology 2 (SH2) domain, inositolpolyphosphate 5-phosphatase activity, three NXXY motifs, several proline-rich regions, and is called SHIP. Mutation of the conserved tyrosine or leucine residues within the FcepsilonRI beta or gamma ITAMs eliminates SHIP binding and indicates that the SHIP-ITAM interaction is specific. SHIP also binds to ITAMs from the CD3 complex and T cell receptor zeta chain in vitro. SHIP protein possesses both phosphatidylinositol-3,4,5-trisphosphate 5'-phosphatase and inositol-1,3,4,5-tetrakisphosphate 5'-phosphatase activity. Phosphorylation of SHIP by a protein-tyrosine kinase, Lck, results in a reduction in enzyme activity. FcepsilonRI activation induces the association of several tyrosine phosphoproteins with SHIP. SHIP is constitutively tyrosine-phosphorylated and associated with Shc and Grb2. These data suggest that SHIP may serve as a multifunctional linker protein in receptor activation.

Animals

Inorganic fluoride concentration after long-term sedation with isoflurane.

We report on five patients in whom long-term sedation with isoflurane for up to 7 days was used successfully. Serum inorganic fluoride concentrations were measured daily. The concentrations ranged from 12 mmol l-1 to 29 mmol l-1. These were well below the described renal toxic level of 50 mmol l-1. There was no deterioration in renal function attributable to the use of isoflurane.

Adult

Role of magnetic resonance imaging in the diagnosis of osteomyelitis in diabetic foot infections.

PURPOSE: The role of magnetic resonance imaging (MRI) in the diagnosis of osteomyelitis in foot infections in diabetics was investigated. The accuracy, sensitivity, and specificity of MRI, plain radiography, and nuclear scanning were determined for diagnosing osteomyelitis, and a cost comparison was made. METHODS: Twenty-seven patients with diabetic foot infections were studied prospectively. All patients underwent MRI and plain radiography. Twenty-two patients had technetium bone scans, and 19 patients had Indium scans. Nineteen patients had all four tests performed. Patients with obvious gangrene or a fetid foot were excluded. RESULTS: The diagnosis of osteomyelitis was established by pathologic specimen (n = 18), bone culture (n = 3), or successful response to medical management (n = 6). Osteomyelitis was confirmed in nine of the pathologic specimens. The diagnostic sensitivity, specificity, and accuracy for MRI was 88%, 100%, and 95%, respectively, for plain radiography it was 22%, 94%, and 70%, respectively, for technetium bone scanning it was 50%, 50%, and 50%, respectively, and for Indium leukocyte scanning it was 33%, 69%, and 58%, respectively. The data were analyzed statistically with the two-tailed Fisher's exact test. MRI was the only test that was statistically significant (p < 0.01). CONCLUSIONS: MRI appeared to be the single best test for the diagnosis of osteomyelitis associated with diabetic foot infections. It had a better diagnostic accuracy than conventional modalities and appeared to be more cost-effective than the frequently used Indium scan.

Adult

Carotid artery stenosis: preoperative noninvasive evaluation in a community hospital.

PURPOSE: The purpose of this study was to determine whether noninvasive evaluation with duplex ultrasonography and magnetic resonance angiography of patients with carotid artery stenosis can replace contrast angiography at our institution. METHODS: This study consisted of a retrospective chart review of 40 patients (74 carotid arteries) in combination with a blinded reanalysis of original data. Contrast angiography was compared with duplex ultrasonography and magnetic resonance angiography. The overall diagnostic accuracy of duplex ultrasonography and magnetic resonance angiography was determined individually and concordantly in patients being evaluated for carotid artery stenosis. RESULTS: The overall sensitivity of duplex ultrasonography was 88.5%, and the specificity was 91.7% (Spearman correlation coefficient = 0.8456; p < 0.001). For magnetic resonance angiography the sensitivity was 92.3%, and the specificity was 97.9% (Spearman correlation coefficient = 0.9086; p < 0.001). In the presence of concordance, the noninvasive studies exhibited a sensitivity of 100%, (correlation coefficient = 0.9661; kappa value = 0.9655). No occlusions or severe lesions were missed by both studies. In only one vessel (1.52%) was a false-positive concordance noted. CONCLUSIONS: Carotid endarterectomy may be undertaken with a high degree of confidence that the operation will be appropriate if the noninvasive evaluations are concordant. In the absence of concordance of the noninvasive studies, contrast angiography should be considered.

Aged

Nuf2, a spindle pole body-associated protein required for nuclear division in yeast.

The NUF2 gene of the yeast Saccharomyces cerevisiae encodes an essential 53-kd protein with a high content of potential coiled-coil structure similar to myosin. Nuf2 is associated with the spindle pole body (SPB) as determined by coimmunofluorescence with known SPB proteins. Nuf2 appears to be localized to the intranuclear region and is a candidate for a protein involved in SPB separation. The nuclear association of Nuf2 can be disrupted, in part, by 1 M salt but not by the detergent Triton X-100. All Nuf2 can be removed from nuclei by 8 M urea extraction. In this regard, Nuf2 is similar to other SPB-associated proteins including Nufl/SPC110, also a coiled-coil protein. Temperature-sensitive alleles of NUF2 were generated within the coiled-coil region of Nuf2 and such NUF2 mutant cells rapidly arrest after temperature shift with a single undivided or partially divided nucleus in the bud neck, a shortened mitotic spindle and their DNA fully replicated. In sum, Nuf2 is a protein associated with the SPB that is critical for nuclear division. Anti-Nuf2 antibodies also recognize a mammalian 73-kd protein and display centrosome staining of mammalian tissue culture cells suggesting the presence of a protein with similar function.

Amino Acid Sequence

Magnetic resonance imaging in the evaluation of persistent carpal tunnel syndrome.

Magnetic resonance imaging was used to assess nine median nerves in the wrists of seven patients who had signs and symptoms of persistent compressive median neuropathy despite previous carpal tunnel release. Intraoperative findings were then correlated in eight surgically treated cases with both MRI findings and postoperative results. Magnetic resonance imaging suggested a potential abnormality in each of eight operative cases. These findings correlated very well with both intraoperative observations and postoperative results, which indicated that some abnormality involving either the median nerve or the transverse carpal ligament had been present in all cases. Magnetic resonance imaging proved to be a sensitive and specific tool in the evaluation of persistent postoperative median nerve compression.

Adult

Maternal-fetal outcomes in prolonged pregnancy.

The intrapartum fetal heart rate changes, type of labor, mode of delivery, and neonatal outcome were evaluated in 379 consecutive continuously monitored prolonged pregnancies (greater than 42 weeks by history and early examination). These represent only a fraction of the total prolonged gestation population. There were 56% multiparous women, 33% less than 20 years of age, and 95% with cephalic presentation. Oxytocin was given to 76% (48% induced, 28% enhanced). Delivery was by cesarean section in 13% of patients (9% of induced cases), and 15% had forceps deliveries. Fetal heart rate alterations were observed in high proportion. Cesarean section for cephalopelvic disproportion was indicated in 60% of operations, and 13% of the fetuses weighed greater than 4000 gm. Depression occurred in 15% of infants at 1 minute and in 4% at 5 minutes. Prolonged hospital stay was seen in 9%, and postmaturity syndrome in 19%. There were four perinatal deaths (two corrected). Active induction does not appear to increase the cesarean section rate. The durations of predelivery observation may be longer because the cervices are frequently unripe. There is a high incidence of fetal heart rate alterations. Induction appears justified as an active intervention to prevent some sudden unexplained deaths.

Adolescent

Yeast proteins that recognize nuclear localization sequences.

A variety of peptides can mediate the localization of proteins to the nucleus. We have identified yeast proteins of 70 and 59 kD that bind to nuclear localization peptides of SV-40 T antigen, Xenopus nucleoplasmin, and the yeast proteins Ga14 and histone H2B. These proteins are assayed by the binding of peptide-albumin conjugates to proteins immobilized on nitrocellulose filters. These binding proteins fractionate with nuclei and are extractable with salt but not detergent. Radiolabeled peptide-albumin conjugates also bind to isolated nuclei; the binding is saturable and can be extracted with salt. Different nuclear localization peptides compete with each other, implying that a single class of proteins is responsible for their recognition. The 70- and 59-kD proteins have the properties expected for a receptor that would act to direct proteins to the nucleus.

Amino Acid Sequence

The efficacy of tilted axial MRI of the CNS.

The angle between the straight axial plane and the orbito-meatal line was measured in 156 consecutive magnetic resonance examinations. Inconsistent head positioning caused this angle to vary by as much as 44 degrees. Careful positioning of the patient by the technologist can minimize this variability, leading potentially to improved image interpretation. To assess the merit of a standardized orientation for MR examinations of the head, straight axial and tilted axial MR scans were compared in 34 patients. The tilted images were obtained parallel to the orbitomeatal line and were found to be superior for visualization of the cerebellum. When correlative x-ray CTs are available or when an abnormality in the posterior fossa is suspected, tilted axial MR scans should be employed.

Brain Diseases