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Biomedical subjects

M Mitchell

Publications and source records attributed to M Mitchell.

At least 73 records · Page 4Linked to original sources

Outcomes of research consortium project.

In previous articles, 1-3 the authors described the evolution and activities of the consortium project, a unique collaborative model for facilitating the conduct of nursing research in service settings. The authors' aim in these articles was to provide information useful to nursing administrators as they fulfill their professional obligation to support and foster the involvement of their staff in nursing research activities. Now, after five years of funding, the chronicle of this project's development, its successes, and difficulties would be incomplete without a final report of the experience. Therefore, this article describes the last two years of the consortium project.

Clinical Nursing Research

Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing.

Australine [(1R,2R,3R,7S,7aR)-3-(hydroxymethyl)-1,2,7-trihydroxypyrrolizid ine] is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis [Molyneux et al. (1988) J. Nat. Prod. (in press)]. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, we tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the alpha-glucosidase amyloglucosidase (50% inhibition at 5.8 microM), but it did not inhibit beta-glucosidase, alpha- or beta-mannosidase, or alpha- or beta-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc3Man7-9(GlcNAc)2-oligosaccharides.

Alkaloids

Differences between the sexes and the effects of surgery and anesthesia on the urinary excretion rate of eicosinoids in the rat.

Measurements were made of PGE2, PGF2 and TXB2 in the urine of male and female Munich-Wistar rats. Initial urine were collected in the awake state in metabolic cages and were followed by collections of ureteral urine during surgery and anesthesia both before and during cyclooxygenase inhibition with indomethacin. The excretion rate of all eicosinoids in the awake state was similar between the sexes. PGE2 excretion remained unaffected after anesthesia/surgery in both sexes indicating that providing plasma volume is maintained, the PGE2 system is not activated by the stress of anesthesia/surgery. Near complete inhibition of PGE2 was observed during indomethacin administration in both sexes. TXB2 excretion rates rose in both males and females with anesthesia/surgery and were slightly suppressed during indomethacin in males only. PGF2 excretion rose following surgery/anesthesia and was statistically significant in female rats. During indomethacin, TXB2 excretion was moderately reduced in male rats and unaffected in the female. Near complete inhibition of PGF2 was observed during indomethacin in both sexes. The urinary eicosinoid responses to indomethacin seen in these studies failed to provide an explanation for our earlier observations of a fall in renal vascular resistance in the female rat, studied under anesthesia and during indomethacin administration.

Anesthesia

The use of an emergency department observation unit in the management of abdominal trauma.

Diagnostic peritoneal lavage (DPL) is a valuable triage tool in the evaluation of patients with abdominal trauma. Observation after a negative lavage is necessary to detect injuries not well discerned by DPL performed in the early postinjury period. We evaluated the use of 12 hours of monitoring in an emergency department observation unit in the management of 230 patients with abdominal trauma and a negative initial DPL. One hundred five of the patients had blunt and 125 had penetrating trauma. One hundred eighty-seven patients (81%) were discharged home from the observation unit without any reported significant complications. Thirty-eight patients (17%) required admission to our hospital; four of the 38 underwent necessary laparotomy. In the 230 patients evaluated, no deaths or complications could be assigned to the use of 12 hours of observation in the unit. The use of an observation unit in our study resulted in the potential savings of $51,329. Our study supports the concept that selected patients with significant abdominal trauma and a negative DPL can be managed safely and cost effectively in an ED observation unit.

Abdominal Injuries

Abnormal diurnal weight gain among chronically psychotic patients contrasted with acutely psychotic patients and normals.

We found diurnal weight gain to be abnormal among 28 institutionalized chronically psychotic patients. They were weighed daily for 15 days at 7 a.m. and 4 p.m. We normalized the diurnal weight gain (NDWG) as a percentage by subtracting the 7 a.m. weight from the 4 p.m. weight, multiplying the difference by 100, and then dividing the result by the 7 a.m. weight. NDWG was 2.8 +/- 1.3% for the 28 study patients, 0.631 +/- 0.405% for 16 acutely psychotic controls, and 0.511 +/- 0.351% for 29 normals. Ninety-three per cent of the study sample had NDWG values above the upper limit of normal. Sex, diagnosis, smoking, baseline weight, blood pressure, and pulse did not explain these observations. NDWG related (N = 28, r = 0.552, P = 0.002) to antipsychotic drug dose. The implications of our findings are discussed.

Adult

Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance.

To evaluate the possibility of administering therapeutic proteins via the respiratory route, we administered an aerosol of recombinant DNA-produced human alpha 1-antitrypsin (rAAT) to anesthetized sheep and measured levels of the protein in epithelial lining fluid (ELF), lung lymph, blood, and urine. Using a nebulizer that generated aerosol droplets with a mass median aerodynamic diameter of 2.7 micron (55% of droplets were less than 3 micron, a particle size optimal for deposition on the alveolar epithelium), in vitro studies demonstrated that the aerosolized rAAT remained intact and fully functional as an inhibitor of neutrophil elastase. When aerosolized to sheep, the 45-kDa rAAT molecule diffused across the alveolar epithelium, as evidenced by its presence in lung lymph and in blood. Comparison of ELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with approximately 10-fold concentration differences in each consecutive compartment, respectively. Importantly, evaluation with aerosolized 125I-labeled rAAT demonstrated that the rAAT molecules that reached the lung lymph and the systemic circulation remained intact as a 45-kDa protein. These results demonstrate the feasibility of using aerosolization to the pulmonary epithelial surface to administer sizeable proteins of therapeutic interest, thus circumventing the necessity of the traditional parenteral modes of administration of such molecules.

Absorption

Localization of murine X and autosomal sequences homologous to the human Y located testis-determining region.

Recently a candidate gene for the primary testis-determining factor (TDF) encoding a zinc finger protein (ZFY) has been cloned from the human Y chromosome. A highly homologous X-linked copy has also been identified. Using this human sequence it is possible to identify two Y loci, an X and an autosomal locus in the mouse (Zfy-1, Zfy-2, Zfx and Zfa, respectively). Suprisingly ZFY is more homologous to the mouse X and autosomal sequences than it is to either of the Y-linked loci. Both Zfy-1 and Zfy-2 are present in the Sxr region of the Y but Zfy-2 is absent in the Sxr deletion variant Sxrb (or Sxr") suggesting it is not necessary for male determination. Extensive backcross analyses map Zfa to mouse chromosome 10 and Zfx to a 5-cM interval between anonymous X probe MDXS120 and the tabby locus (Ta). We also show that the mouse androgen receptor locus (m-AR) believed to underlie the testicular feminization mutation (Tfm) shows complete linkage to Zfx. Comparative mapping indicates that in man these genes lie in separate conserved DNA segments.

Animals

Size and physical map of the chromosome of Haemophilus influenzae.

A variation of pulse-field electrophoresis, field-inversion gel electrophoresis, was used to determine the size and physical map of the chromosome of Haemophilus influenzae. The DNA of H. influenzae had a low G + C content (39%) and no restriction sites for the enzymes NotI or SfiI. However, a number of restriction enzymes (SmaI, ApaI, NaeI, and SacII) that recognized 6-base-pair sequences containing only G and C nucleotides were found to generate a reasonable number of DNA fragments that were separable in agarose gels by field-inversion gel electrophoresis. The sizes of the DNA fragments were calibrated with a lambda DNA ladder and lambda DNA restriction fragments. The sum of fragment sizes obtained with restriction digests yielded a value for the chromosome of 1,980 kilobase pairs. Hybridization of a labeled fragment with two or more fragments from a digest with a different restriction enzyme provided the information needed to construct a circular map of the H. influenzae chromosome.

Chromosomes, Bacterial

A team approach to prevocational services.

This paper presents a chronology of legislative mandates for vocational rehabilitation, discusses their impact on occupational therapy, and describes relationships between special educators and vocational agencies. The Career Training Workshop, a prevocational program developed and used successfully by a North Carolina school district, is described here as an example of one effort to prepare students with disabilities for employment.

Activities of Daily Living

Selective inhibition of glycoprotein-processing enzymes. Differential inhibition of glucosidases I and II in cell culture.

In this study, we compared the effects of 2,6-dideoxy-2,6-imino-7-O-(beta-D-glucopyranosyl)-D-glycero-L-gulohep titol (MDL) to those of the glucosidase I inhibitor, castanospermine, on the purified processing enzymes glucosidases I and II. WE also compared the effects of these two inhibitors on glycoprotein processing in cell culture using influenza virus-infected Madin-Darby canine kidney cells as a model system. With the purified processing enzymes, castanospermine was a better inhibitor of glucosidase I than of glucosidase II, whereas MDL is more effective against glucosidase II than glucosidase I. In cell culture at the appropriate dose, MDL also preferentially affected glucosidase II. Thus, at 250 micrograms/ml MDL, the major [3H]glucose-labeled (or [3H]mannose-labeled) glycopeptide from the viral hemagglutinin was susceptible to endoglucosaminidase H, and the oligosaccharide liberated by this treatment was characterized as a Glc2Man7-9GlcNAc on the basis of size, resistance to digestion by glucosidase I (but sensitivity to glucosidase II), methylation analysis, and Smith degradation studies. These data indicate that at appropriate concentrations of MDL (250 micrograms/ml), one can selectively inhibit glucosidase II in Madin-Darby canine kidney cells. However, at higher concentrations of inhibitor (500 micrograms/ml), both enzymes are apparently affected. Since MDL did not greatly inhibit the synthesis of lipid-linked saccharides or the synthesis of protein or RNA, it should be a useful tool for studies on the biosynthesis and role of N-linked oligosaccharides in glycoprotein function.

Alkaloids

Generation of different nucleosome spacing periodicities in vitro. Possible origin of cell type specificity.

We have been able to generate ordered nucleosome arrays that span the physiological range of spacing periodicities, using an in vitro system. Our system (a refinement of the procedure previously developed) uses the synthetic polynucleotide poly[d(A-T)], poly[d(A-T)], core histones, purified H1, and polyglutamic acid, a factor that increases nucleohistone solubility and greatly promotes the formation of ordered nucleosome arrays. This system has three useful features, not found in other chromatin assembly systems. First, it allowed us to examine histones from three different cell types/species (sea urchin sperm, chicken erythrocyte, and HeLa) as homologous or heterologous combinations of core and H1 histones. Second, it allowed us to control the average packing density (core histone to polynucleotide weight ratio) of nucleosomes on the polynucleotide; histone H1 is added in a second distinct step in the procedure to induce nucleosome alignment. Third, it permitted us to study nucleosome array formation in the absence of DNA base sequence effects. We show that the value of the spacing periodicity is controlled by the value of the initial average nucleosome packing density. The full range of physiological periodicities appears to be accessible to arrays generated using chicken erythrocyte (or HeLa) core histones in combination with chicken H5. However, chromatin-like structures cannot be assembled for some nucleosome packing densities in reactions involving some histone types, thus limiting the range of periodicities that can be achieved. For example, H1 histone types differ significantly in their ability to recruit disordered nucleosomes into ordered arrays at low packing densities. Sea urchin sperm H1 is more efficient than chicken H5, which is more efficient than H1 from HeLa or chicken erythrocyte. Sea urchin sperm core histones are more efficient in this respect than the other core histone types used. These findings suggest how different repeat lengths arise in different cell types and species, and provide new insights into the problems of nucleosome linker heterogeneity and how different types of chromatin structures could be generated in the same cell.

Animals

Ultrasonic growth parameters in fetuses of mothers with primary addiction to cocaine.

Sixty-seven women with primary addiction to cocaine were evaluated during their pregnancies by multiple ultrasound studies. Ultrasonic parameters included biparietal diameter, femur length, abdominal circumference, and head circumference. These values were compared with ultrasonic growth parameters in nonaddicted fetuses. Head and abdominal circumference data were used to evaluate the fetuses according to growth pattern. With this system of scoring, subtleties of asymmetric versus symmetric intrauterine growth retardation become apparent. In addition, birth weights of addicted infants were compared with birth weights of nonaddicted infants. The results suggest that, although statistically significant differences in birth weights cannot be demonstrated, abnormal growth of the addicted fetuses does occur. Addicted fetuses show a greater proportion of biparietal diameter and abdominal circumference values below the 50th and 25th percentiles than nonaddicted fetuses, and addicted fetuses more frequently exhibit intrauterine growth retardation patterns. These data suggest that it is fruitful to study these infants with near-normal size but with abnormal intrauterine growth patterns.

Birth Weight

Septic arthritis.

Infectious arthritis is a commonly encountered clinical problem which may result from articular contamination by a wide variety of organisms. Involvement of an articulation may occur by one of four mechanisms: hematogenous spread, spread from a contiguous source of infection, direct implantation, or postoperative contamination. Distribution is typically monoarticular with a swollen, erythematous, and painful joint. The radiographic differential diagnosis includes limited rheumatoid arthritis, gout, synovial osteochondromatosis, and pigmented villonodular synovitis. In order to prevent complications, including growth disturbances, articular destruction with ankylosis, osteomyelitis, or soft tissue extension, early diagnostic arthrocentesis is important. Radiographic abnormalities, which include soft tissue swelling, joint space loss, periarticular osteopenia, and central or marginal osseous erosions, may be delayed following clinical onset of infection. Advanced imaging techniques such as scintigraphy, CT, or MRI may allow accurate diagnosis of the infectious process at an earlier stage.

Arthritis, Infectious

Diagnostic imaging of bone tumors in the foot.

Many tumor and tumor-like lesions may involve bone. Bone tumors in the foot are, however, very rare. An accurate diagnosis relies on a cooperative clinical and imaging effort. The patient's age, sex, history, clinical findings, and presentation, in addition to the radiographic features, allow for proper diagnosis. Specialized imaging techniques may be helpful in certain instances. Aside from a biopsy, the radiograph is clearly the most important single approach to the diagnosis of bone tumors affecting the foot.

Bone Cysts

Arthrography, tenography, and bursography of the ankle and foot.

A brief description of normal anatomy and common arthrographic, tenographic, and bursographic procedures is presented. The described procedures are important diagnostic tools and do not carry major risk. Therefore, these procedures can be performed on an outpatient basis.

Ankle