Biomedical subjects
S Smith
Publications and source records attributed to S Smith.
Gastrocolic fistula. A review of 15 cases and an update of the literature.
Gastrocolic fistulas are not common. We review the 10-year experience in our center of 15 cases that emphasize the changing pattern of this disease. The female-to-male ratio was 2:1, with a mean age of 55. Even though we are affiliated with the regional cancer center, the commonest cause of a fistula was benign gastric ulceration. Sixty percent of those with peptic ulcer and a fistula had not had previous gastric surgery. Barium enema was the most accurate investigation, showing the fistula in 10 of 10. Barium meal showed it in seven of eight, and the fistula was seen in seven of 10 patients who had endoscopy. Eleven patients were operated on, and only one was treated "medically." Three deaths occurred, two from advanced carcinoma and one from myocardial infarction.
Index of suspicion. Case 2. Ankylosing spondylitis.
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Submicrometer intracellular chemical optical fiber sensors.
A thousandfold miniaturization of immobilized optical fiber sensors, a millionfold or more sample reduction, and at least a hundredfold shorter response time, all simultaneously, were achieved by combining nanofabricated optical fiber tips with near-field photopolymerization. Specifically, pH optical fiber sensors were prepared with internal calibration, making use of the differences in both fluorescence and absorption of the acidic and basic dye species. The submicrometer sensors have excellent detection limits, as well as photostability, reversibility, and millisecond response times. Successful applications include intracellular and intraembryonic measurements. Potential applications include spatially and temporally resolved chemical analysis and kinetics inside single biological cells and their substructures.
Utilization of an active serine 101----cysteine mutant to demonstrate the proximity of the catalytic serine 101 and histidine 237 residues in thioesterase II.
Thioesterase II is a 29-kDa monomer which, in certain specialized tissues, acts as a chain terminator in fatty acid synthesis by hydrolyzing medium-chain fatty acids from the fatty acid synthase. As with serine proteases, hydrolysis appears to involve acylation of the active site serine residue (Ser-101) assisted by a histidine, tentatively identified as His-237. To determine whether in the folded protein His-237 is close enough to accept a proton from the Ser-101 hydroxyl, we have made use of a Ser101Cys mutant which retains up to 90% of catalytic activity. Unlike the wild-type enzyme, the S101C thioesterase is inhibited with stoichiometric amounts of the bifunctional alkylating reagent 1,3-dibromopropanone. To facilitate identification of the alkylated residue(s), the keto group introduced into the dibromopropanone-modified S101C mutant was radiolabeled by reduction with sodium [3H] borohydride. The protein was then digested and the radiolabeled peptides analyzed by amino acid sequencing and mass spectrometry. The experimental data unambiguously showed that dibromopropanone cross-linked the active site Cys-101 with His-237, demonstrating that these residues are positioned within 5 A of each other. These data strongly support the hypothesis that in the wild-type thioesterase His-237 accepts a proton from Ser-101, thus increasing its nucleophilic character and improving the catalytic efficiency of the enzyme. The possibility that exchange of cysteine and serine active site residues has occurred in the evolution of thioesterases is discussed.
Immunophenotypic characterization of owl monkey peripheral blood mononuclear cells.
A two-phase study was initiated to delineate the peripheral blood lymphocyte populations present in owl monkeys and to correlate those populations with immune response and parasitism during malaria infection. The goal of phase I of the study was to elucidate a monoclonal antibody panel that could be used to characterize peripheral blood mononuclear cell (PBMC) populations with flow cytometric techniques. Forty-two monoclonal antibodies (reported to be reactive with human and macaque lymphocyte antigens) were screened for activity to owl monkey PBMC. Eleven monoclonals were found to react: anti-H42A (MHC Class II DP-like); anti-TH14B (MHC Class II DR-like); and anti-TH81A5 (MHC Class II DQ-like); anti-H58A (MHC Class I); anti-DH59B (granulocyte and monocyte); anti-B1 (B cell); anti-T4 (CD4); anti-Leu3a (CD4); anti-Leu11a (CD16); anti-60.3 (CD18); and anti-OKM1 (NK and monocyte). In a preliminary retrospective study correlating antibody titers, parasitemia values, and MHC Class I and Class II marker profiles on PBMC to test antigens used in malaria vaccine trials, a significant negative association was observed between cells bearing MHC Class II molecules and the other elements of the comparison. In summary, an appropriate panel of monoclonal antibodies has been identified for characterizing PBMC in owl monkeys, and preliminary studies indicate a possible association between clinical outcome and expressed phenotypic PBMC markers.
Warmer welcomes.
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Serum oncoproteins and growth factors in asbestosis and silicosis patients.
Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.
Insurance and HIV antibody testing.
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Intron-exon organization of the gene for the multifunctional animal fatty acid synthase.
The complete intron-exon organization of the gene encoding a multifunctional mammalian fatty acid synthase has been elucidated, and specific exons have been assigned to coding sequences for the component domains of the protein. The rat gene is interrupted by 42 introns and the sequences bordering the splice-site junctions universally follow the GT/AG rule. However, of the 41 introns that interrupt the coding region of the gene, 23 split the reading frame in phase I, 14 split the reading frame in phase 0, and only 4 split the reading frame in phase II. Remarkably, 46% of the introns interrupt codons for glycine. With only one exception, boundaries between the constituent enzymes of the multifunctional polypeptide coincide with the location of introns in the gene. The significance of the predominance of phase I introns, the almost uniformly short length of the 42 introns and the overall small size of the gene, is discussed in relation to the evolution of multifunctional proteins.
Immunotherapy with a tumor-infiltrating lymphocyte clone, soluble antigen, and cyclophosphamide.
A tumor-specific cytotoxic T-lymphocyte clone derived from bulk cultures of tumor-infiltrating lymphocytes attenuated the outgrowth of methylcholanthrene (MCA)-induced fibrosarcomas in C3H/HeJ mice. In 4-hour chromium 51-release assays, bulk cultures of tumor-infiltrating lymphocytes showed nonspecificity for MCA-induced tumors (MCA-F, MCA-D, MCA-SP), YAC-1, and EL-4. In contrast, a cytotoxic T-lymphocyte-cloned line specifically killed MCA-F, but not MCA-D or MCA-SP. Cytotoxic T-lymphocyte line 8 protected syngeneic hosts in local and systemic adoptive transfer assays. Hosts bearing 4-day-established MCA-F tumor cells received single agents or combinations of isoelectrophoretically purified butyl alcohol-extracted tumor-specific transplantation antigen (1 microgram/wk), cyclophosphamide (20 mg/kg on days 4 and 11), and/or cytotoxic T-lymphocytes (1 x 10(7) cells on days 7 and 14). While the mean tumor diameter was 11.6 +/- 1.3 mm in untreated hosts or after single treatments, the combination of tumor-specific transplantation antigen and cyclophosphamide along with the cytotoxic T-lymphocyte clone resulted in tumor diameters of 1.8 +/- 0.5 mm. The triple combination prolonged host survival from 39.6 +/- 1.6 to 57.2 +/- 4.7 days compared with antigen and cyclophosphamide treatment.
Superoxide generation by the human polymorphonuclear leukocyte in response to latex beads.
In this study, superoxide formation was not immediately detected when polymorphonuclear leukocytes were treated with linoleyl alcohol-coated, carboxy-modified latex beads. However, all other measures of neutrophil activation were present. Superoxide was not detected until 30 min after the initial exposure to beads. However, an O2(-)-producing, NADPH-dependent oxidase is active 15 min after exposure. When polymorphonuclear leukocytes are pretreated with cytochalasin B, superoxide production is detected immediately after exposure to the beads. Superoxide secretion after treatment with linoleyl alcohol-coated latex beads is compared with the response to other latex beads. The results imply that neutrophils form a phagolysosome around linoleyl alcohol-coated latex beads that is tightly sealed and does not allow superoxide to escape into the medium where it could be detected by the reduction of ferricytochrome c.
Effect of weather variables on methyl parathion disappearance from cotton foliage.
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Rapid PCR-based construction of specifically enriched libraries from small retina samples.
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Blockade of protein C activation reduces microvascular surgical blood loss.
Protein C is a natural anticoagulant glycoprotein which prevents intravascular clot formation. Protein C functions as an anticoagulant when converted to an active serine protease (activated protein C). Activated protein C is formed at the site of the endothelial injury in response to blood clotting and helps limit the size of blood clots. We tested the hypothesis that by temporarily blocking the activation of intrinsic protein C, we could reduce subsequent surgical blood loss from a microvascular surgical wound. The formation of activated protein C was blocked systemically by intravenous administration of a monoclonal antibody (HPC4) which binds to circulating protein C and prevents its conversion to activated protein C. Domestic pigs were blindly pretreated with intravenous HPC4 or saline then underwent partial-thickness skin graft harvesting to create a reproducible microvascular wound. Blood loss was measured from each wound and the hemostatic effect of protein C blockade was compared to intravenous saline alone as well as to topical thrombin or thromboplastin. We found that blocking the activation of protein C significantly (P = 0.005) reduces surgical blood loss in this model by 27% compared to saline control animals. Intravenous HPC4 performed equally as well as topical thrombin or tissue thromboplastin. In addition, topical thrombin acted synergistically with HPC4 to reduce blood loss an additional 44% (P = 0.01) as compared to intravenous HPC4 or topical thromboplastin alone. Autopsies performed 1 week after HPC4 treatment showed no evidence of systemic thrombosis resulting from the protein C blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Computed tomography of primary transitional cell carcinoma of upper urinary tracts.
Preoperative computed tomography (CT) was utilized to evaluate 20 patients with primary transitional cell carcinoma of the upper urinary tracts. Of the 20 patients, 18 (90%) had CT visualization of the tumor as either a discrete mass or local ureteral and/or renal pelvic wall thickening; 2 (10%) had false-negative examinations. Seven of the 20 patients (35%) had CT evidence of tumor extension demonstrated by frank tumor invasion beyond the urothelium or by perirenal pelvic and/or periureteral fat streaks. Of the 4 patients with fat streaks, 2 (50%) had superficial tumors (T(A)T2), 1 had a T1 (25%) tumor, and 1 had a T3 (25%) tumor. All 3 patients with CT findings of direct extension of tumor through the wall of the ureter or renal pelvis had T3 tumors. Among the 13 with localized noninvasive tumor on CT, 5 (38%) had superficial tumors (TA, TIS, T1), 5 (38%) had T2 tumors, and 3 (21%) had T3 tumors. Of the 5 patients with enlarged regional lymph nodes (greater than or equal to 1.5 cm) on CT, 2 had tumor confirmed histologically, 2 had subsequent negative CT-guided biopsies, and 1 had a negative lymphadenectomy. Distant metastasis was discovered in 1 patient. The data suggest that when CT demonstrates direct tumor extension through the renal pelvic or ureteral wall, it is a sensitive indicator of high-stage disease. However, in the absence of this finding, CT is of limited value in staging patients with primary transitional cell carcinoma of the pyeloureteral system.
Acute effects of intravenous phosphodiesterase inhibition in chronic heart failure: simultaneous pre- and afterload reduction with a single agent.
Intravenous phosphodiesterase inhibition with milrinone is known to have a beneficial effect on haemodynamics in chronic heart failure. Its effect on lower limb capacitance vessels has not been previously investigated. We have studied the effect of intravenous milrinone in 10 patients with severe chronic heart failure. Thirty minutes after commencement of treatment mean cardiac index had risen by 26% and pulmonary artery wedge pressure, systemic vascular resistance and right atrial pressure had fallen by 51, 24 and 89%, respectively (p less than 0.05 for all changes). These changes were maintained for the 2 h observation period with no evidence of tolerance and were accompanied by a 17% increase in venous volume (p less than 0.01) and a 42% increase in ejection fraction (p less than 0.001) at 30 min; at 120 min the improvement in ejection fraction had been maintained and a further increase in venous volume to 38% above baseline was evident. The increase in venous volume was strongly correlated with the decrease in mean pulmonary artery wedge pressure and mean right atrial pressure at 30 min and 2 h (r = -0.80 and -0.69 for mean pulmonary artery wedge pressure, r = -0.88 and -0.56 for mean right atrial pressure). Milrinone therefore has clinically important venodilating properties, in addition to its known effects as an arterial vasodilator and a positive inotrope.
Perceived competence in cardiopulmonary resuscitation, knowledge and skills, amongst 50 qualified nurses.
50 qualified nurses were surveyed regarding their perception of their competence in resuscitation and cardiology-related skills. This included the ability to place a patient on a cardiac monitor, the identification of 7 basic arrhythmias and the ability to offer correctly to the anaesthetist the equipment for airway intubation and central venous cannulation during the cardiac arrest situation. Generally, there was not a satisfactory level of knowledge, with only 10 nurses (20%) feeling competent in identifying all 7 basic arrhythmias. 33 nurses (66%) believed that they were competent in handling the anaesthetist the correct equipment for intubation, but only 22 nurses (44%) stated competence in offering the correct equipment for central venous cannulation. A review of the literature reveals that there is a considerable disparity between perceived competence and the actual ability to carry out the resuscitation skills. This survey once again reinforces the urgent need for regular assessment and updating of resuscitation skills, knowledge and practice amongst nurses, particularly those working in the ward areas.