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Biomedical subjects

M Shaffer

Publications and source records attributed to M Shaffer.

At least 19 recordsLinked to original sources
PubMed2000

Outcome of patients receiving photodynamic therapy for early esophageal cancer.

PURPOSE: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer. METHODS AND MATERIALS: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months). RESULTS: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy. CONCLUSION: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Antineoplastic Agents↗
PubMed1998

Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation.

This study describes the metabolic, morphologic, neurologic, and functional adaptations observed in the plantar flexors during 8 weeks of lower leg immobilization and 10 weeks of physical therapy following ankle surgery. A combination of magnetic resonance imaging and spectroscopy, isokinetic and isometric muscle testing, and simple functional tests revealed many adaptive changes due to immobilization, including atrophy, loss of muscle strength, reduced central activation, increase in fatigue resistance, and an increase in inorganic phosphate content. After 10 weeks of physical therapy all alterations were reversed, with the exception of a remaining 5.5% deficit in total muscle cross-sectional area.

Adult↗
PubMed1997

A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs.

We report the purification, molecular cloning, and expression of a novel cytosolic calcium-independent phospholipase A2 (iPLA2) from Chinese hamster ovary cells, which lacks extended homology to other phospholipases. iPLA2 is an 85-kDa protein that exists as a multimeric complex of 270-350 kDa with a specific activity of 1 micromol/min/mg. The full-length cDNA clone encodes a 752-amino acid cytoplasmic protein with one lipase motif (GXS465XG) and eight ankyrin repeats. Expression of the cDNA in mammalian cells generates an active 85-kDa protein. Mutagenesis studies show that Ser465 and the ankyrin repeats are required for activity. We demonstrate that iPLA2 selectively hydrolyzes the sn-2 over sn-1 fatty acid by 5-fold for 1,2-dipalmitoyl phosphatidylcholine in a mixed micelle. Moreover, we found the fatty acid preference at the sn-2 position to be highly dependent upon substrate presentation. However, iPLA2 does have a marked preference for 1,2-dipalmitoyl phosphatidic acid presented in a vesicle, generating the lipid second messenger lysophosphatidic acid. Finally the enzyme is able to hydrolyze the acetyl moiety at the sn-2 position of platelet-activating factor.

Amino Acid Sequence↗
PubMed1993

Salmonella poona infection and surveillance in a neonatal nursery.

BACKGROUND: This article reports the first known outbreak of Salmonella poona infection in a neonatal unit. Three babies had stool cultures positive for the organism. At the same time, S. poona was the cause of a nationwide food-borne outbreak associated with contaminated canteloupe. To minimize the neonatal outbreak, surveys were performed and control measures were instituted. METHODS: Epidemiologic surveillance included the culture of rectal swabs collected from 48 employees, 18 babies, and four family members of the babies. Control measures used included the placement in cohorts and isolation of infected babies, strict adherence to universal precautions, and the restriction of visitation in the nursery. RESULTS: A total of three babies and one employee in the surveillance were found to have Salmonella sp. An additional two hospitalized adult patients had S. poona. Of all the people included in the surveillance, only the three babies were found to have S. poona. The hospital employee had S. enteritidis. CONCLUSIONS: Timely culture results, rapid cohort placement of infected babies, and strict adherence to universal precautions led to the successful eradication of the organism.

Adult↗
PubMed1992

Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density.

Carbohydrate recognition by the human endothelial-leukocyte adhesion molecule, E-selectin, has been investigated by binding studies using 3H-labeled Chinese hamster ovary cells expressing different levels of the transfected full-length adhesion molecule and a series of structurally defined oligosaccharides linked to the lipid phosphatidylethanolamine dipalmitoate (neoglycolipids) and synthetic glycolipids chromatographed on silica gel plates or immobilized on plastic wells. Evidence is presented for density-dependent binding of the membrane-associated E-selectin not only to 3'-sialyl-lacto-N-fucopentaose II (3'-S-LNFP-II) and 3'-sialyl-lacto-N-fucopentaose III (3'-S-LNFP-III) which express the sialyl Le(a) and sialyl Le(x) antigens, respectively, but also to the nonsialylated analogue LNFP-II; there is a threshold density of E-selectin required for binding to these sialylated sequences, and binding to the nonsialylated analogue is a property only of cells with the highest density of E-selectin expression. The presence of fucose linked to subterminal rather than to an internal N-acetylglucosamine is shown to be a requirement for E-selectin binding, and although the presence of sialic acid 3-linked to the terminal galactose of the LNFP-II or LNFP-III sequences substantially enhances E-selectin binding, the presence of 6-linked sialic acid abolishes binding. E-selectin binding is unaffected in the presence of the blood group H fucose (alpha 1-2 linked to galactose to form the Le(b) antigen). However, the binding is abolished when in addition alpha 1-3-linked N-acetylgalactosamine to the galactose (blood group A antigen) is present. These results indicate that some E-selectin-mediated adhesive events may be influenced by blood group status.

Animals↗
PubMed1992

P-selectin and E-selectin. Distinct but overlapping leukocyte ligand specificities.

P-selectin on platelets and endothelial cells and E-selectin on endothelial cells are leukocyte receptors that recognize lineage-specific carbohydrates on neutrophils and monocytes. The proposed ligands for these receptors contain the Le(x) core and sialic acid. Since other investigators have shown that both E-selectin and P-selectin bind to sialylated Le(x), we evaluated whether E-selectin and P-selectin recognize the same counter-receptor on leukocytes. The interaction of HL60 cells with Chinese hamster ovary (CHO) cells expressing P-selectin or E-selectin was studied. To determine whether a protein component is required in addition to sialyl Le(x) for either P-selectin or E-selectin recognition, HL60 cells or neutrophils were digested with proteases, including chymotrypsin, elastase, proteinase Glu-C, ficin, papain, or thermolysin. Cells treated with these proteases bound E-selectin but not P-selectin. Fucosidase or neuraminidase treatment of HL60 cells markedly decreased binding to both E-selectin- and P-selectin-expressing CHO cells. Growth of HL60 cells in tunicamycin inhibited the ability of these cells to support P-selectin-mediated binding and, to a lesser extent, E-selectin-mediated binding. Purified P-selectin inhibited CHO:P-selectin binding to HL60 cells, but incompletely inhibited CHO:E-selectin binding to HL60 cells. However, purified soluble E-selectin inhibited CHO:P-selectin and CHO:E-selectin binding to HL60 cells equivalently and completely. COS cells, unable to bind to E-selectin or P-selectin, bound E-selectin but not P-selectin upon transfection with alpha-1,3-fucosyltransferase or alpha-1,3/1,4-fucosyltransferase. Similarly, LEC 11 cells expressing sialyl Le(x) bound E-selectin- but not P-selectin-expressing CHO cells. Sambucus nigra lectin, specific for the sialyl-2,6 beta Gal/GalNAc linkage, inhibited P-selectin but not E-selectin binding to HL60 cells. Although sialic acid and Le(x) are components of the P-selectin ligand and the E-selectin ligand, these results indicate that the ligands are related, having overlapping specificities, but are structurally distinct. A protein component containing sialyl Le(x) in proximity to sialyl-2,6 beta Gal structures on the P-selectin ligand may contribute to its specificity for P-selectin.

Animals↗
PubMed1991

Clinical engineering in today's hospital: perspectives of the administrator and the clinical engineer.

In 1987-88, the first of two surveys conducted questioned the administrator's viewpoint on choice of reporting authority for plant operations and clinical engineering departments as well as the job satisfaction and prestige associated with these responsibilities. The second tested the response of clinical engineers on similar issues as well as the effect of certain organizational factors on their degree of functional involvement in the equipment-management process. In the first survey, two-thirds of the administrators chose a structure that, as shown in the second survey, leads to a higher degree of involvement and satisfaction for clinical engineers. Other organizational factors that have an effect are: the type of hospital (teaching and nonteaching), the presence of qualified university-degree engineers, and ensuring that the clinical engineering role within the health care institution is recognized and supported. Teaching hospitals are found to provide a better climate than nonteaching ones for the support of the research and education activities. Clinical engineering departments, whose role has been recognized and supported by their institution, are more substantially involved in all aspects of the equipment-management process than those who are still seeking this recognition. Finally, departments where university-degree engineers have been hired again show more involvement and commitment to the quality and efficiency of their operation.

Attitude of Health Personnel↗
PubMed1989

Membrane filtration differentiation of E. coli from coliforms in the examination of water.

A membrane filter-Endo agar method for enumerating Escherichia coli as distinct from other coliforms in drinking water was developed. Membranes containing coliform colonies are transferred to nutrient agar containing 4-methyl umbelliferyl-beta-D-glucuronide (MUG) and incubated at 35 degrees C for 4 h. The MUG is hydrolyzed by the glucuronidase of E. coli and the fluorogenic product is visualized. The method recovered 98% of E. coli without false positives and is proposed as an additional test in routine water examination for the detection of pollution.

Colony Count, Microbial↗
PubMed1986

Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation.

Protein S is a cofactor of activated protein C; together they function as a regulator of blood coagulation. A human liver cDNA library constructed in bacteriophage lambda gt11 was screened with DNA fragments from a full-length bovine cDNA clone encoding protein S. Several cDNA clones were isolated and sequenced. The combined cDNA sequences encoded the mature protein and 15 residues of the leader sequence when compared to bovine protein S. Human protein S is a single-chain protein consisting of 635 amino acids with 82% homology to bovine protein S. After an NH2-terminal gamma-carboxyglutamic acid-containing region, there is a short region with thrombin-sensitive bond(s), followed by a region with four repeat sequences that are homologous to the precursor of mouse epidermal growth factor. In contrast to the other vitamin K-dependent plasma proteins, the COOH-terminal portion of human protein S does not show any resemblance to serine proteases.

Amino Acid Sequence↗
PubMed1984

Treatment of experimental chronic osteomyelitis caused by Morganella morganii with mezlocillin and cloxacillin.

Mezlocillin was used alone and in combination with cloxacillin in the treatment of chronic experimental osteomyelitis due to Morganella morganii. This combination showed in vitro synergy as measured by the checkerboard technique. A marked inoculum affect was demonstrated in vitro with mezlocillin and the infecting strain of M. morganii. In therapeutic trials, mezlocillin administered for 28 days was totally ineffective. The combination of mezlocillin and cloxacillin (at 800 and 400 mg/kg, respectively, 4 times a day) given for 28 days was significantly better than either no therapy or therapy with mezlocillin alone. However, even after 4 weeks of combined therapy with mezlocillin and cloxacillin M. morganii was recovered from the bones of 55% of the treated rabbits.

Animals↗