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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 559 records · Page 31Linked to original sources

The elasticity of uniform, unilamellar vesicles of acidic phospholipids during osmotic swelling is dominated by the ionic strength of the media.

Uniform, unilamellar vesicles have been prepared by the pH-modification technique. The initial sizes of the vesicles were from 200 to 700 nm and were measured to within 1-3% by photo correlation spectroscopy. Vesicles were made of the dioleoyl esters of phosphatidic acid, phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, the diphytanyl ethers of phosphatidylglycerol, Escherichia coli lipids, and lac permease reconstituted into E. coli lipids. The vesicle suspensions were prepared and then diluted with electrolyte (KCl) and/or nonelectrolyte (sucrose, trehalose, pentaerythritol) impermeants. The amplitude of the swelling is linearly proportional to the osmotic pressure difference across the bilayer. We have determined the elastic modulus, the elastic limit (percent surface expansion at bursting), and the transbilayer pressure difference at bursting for each of these vesicles at constant osmolarity but at different ionic strengths. We find that the elastic properties of the bilayer vary by a factor of 10 in electrolyte media as compared to isosmolal nonelectrolyte media and that this variation appears to be related to both the charge density at the surface and the ionic strength of the media. Anionic lipid vesicles in 150 mM KCl have a significantly higher modulus (50 X 10(7) dyn/cm2) and transbilayer pressure difference (40 mosM) at bursting with a small capacity to stretch (3-4% surface expansion) compared to the same vesicles suspended in nonelectrolyte impermeants. The latter vesicles undergo a significant surface expansion (8-10%), display a low modulus (3 X 10(7) dyn/cm2), and burst at 3-4 mosM bilayer pressure difference. Vesicles suspended in media of constant osmolarity at various ionic strengths display properties with proportional values.(ABSTRACT TRUNCATED AT 250 WORDS)

Elasticity↗

ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum, is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa glucose regulated protein (GRP94).

We have isolated an expressible full-length cDNA clone encoding murine ERp99, an abundant, conserved transmembrane glycoprotein of the endoplasmic reticulum membrane. ERp99 is synthesized as a 92,475-kDa precursor containing 802 amino acids. It possesses a signal peptide of 21 amino acids which is cleaved cotranslationally. Analysis of the amino acid sequence deduced from the nucleotide sequence of the cDNA clone led us to propose a model for the orientation of ERp99 in the endoplasmic reticulum membrane. In this model, ERp99 possesses one membrane-spanning, stop transfer segment in the N-terminal region. The protein chain passes through the membrane only once, and approximately 75% of the protein remains on the cytoplasmic side of the ER membrane. Comparison of the ERp99 sequence to the sequence of other proteins revealed that ERp99 has extensive homology with the 90-kDa heat shock protein of Saccharomyces cerevisiae (hsp90) and the 83-kDa heat shock protein of Drosophila melanogaster. In addition, the N terminus of mature ERp99 is identical to that of the 94-kDa glucose regulated protein (GRP94) of mammalian cells.

Amino Acid Sequence↗

Collagen fibre orientation in bovine secondary osteons by collagenase etching.

The orientation of collagen fibres in bovine secondary osteons has been investigated in the scanning electron microscope (SEM) by removal independently of firstly the mineral component and secondly the collagen fibres. Demineralization of polished transverse sections reveals a lamellar structure for the collagen component but the precise orientation of the collagen in each ring is not unequivocably determined. However, by using a collagenase solution to etch away the collagen component of a polished surface, holes are produced in the mineral revealing the former position of the fibres. The greater rigidity of the mineral component ensures that the structure does not collapse and produce artifacts. A specimen cut so that transverse and longitudinal sections are simultaneously observed allows the relationship between the structural features on each surface to be revealed. Analysis of such micrographs indicates a model for the collagen component of osteons in which the lamellar structure contains fibres with orientations alternately parallel to and circumferential to the long axis of the osteon. Tilting the samples to look directly down the holes shows that the fibres are not precisely longitudinal and circumferential but are tilted from these ideals by a variable angle (typically 20 degrees) the precise angle probably being an important factor related to the in vivo mechanical property requirements.

Animals↗

Accelerated radiotherapy followed by chemotherapy for locally recurrent small-cell carcinoma of the lung. A phase II study of Cancer and Leukemia Group B.

Recurrent or persistent small-cell carcinoma of the lung (SCCL) after chemotherapy (CT) alone has shown a poor response to conventional salvage radiotherapy (RT). Accelerated RT is judged more effective than conventional RT for rapidly growing tumors such as SCCL. The objectives of this study were: to determine the tolerability of accelerated RT; and to test the ability of accelerated RT plus CT to achieve local tumor control (LTC) of SCCL recurrent after CT. Patients whose localized tumor was not controlled were selected from Arm III of the Cancer and Leukemia Group B (CALGB) protocol 8083 (Proc. ASCO 2:230, 1984) as eligible for this study. The program of accelerated RT consisted of the delivery of 50.1 Gray (Gy) in 30 fractions over a period of 21 days to the chest. New chemotherapy different from the first began 2 weeks after the completion of RT and was repeated every 3 weeks for 18 months (M). Of 29 potentially eligible patients with locally recurrent SCCL after the first line CT alone from Arm III of the CALBG protocol 8083, 12 were enrolled initially in this study. The analysis of LTC included 11 patients excluding one patient who died 4 weeks after the start of RT from liver metastases. The LTC achieved was as follow: complete remission in 8/11 (72%) and partial remission in 3/11 patients. None of the patients was converted to CR by subsequent chemotherapy. Survival ranged from 2 to 20 M, with a median survival time of 6 M. Tolerance to the subsequent CT, normal tissue reaction to accelerated RT, and the theoretical advantage of accelerated RT over conventional RT for SCCL were evaluated.

Aged↗

Fungal peritonitis during continuous ambulatory peritoneal dialysis: a report of 17 cases.

Seventeen cases of fungal peritonitis and one case of Nocardia asteroides peritonitis were observed in 141 patients during the first 5 years of our continuous ambulatory peritoneal dialysis program (CAPD). Fungal peritonitis accounted for 7% of the episodes of peritonitis observed in this interval. There were eight deaths associated with fungal peritonitis. In only three instances could factors predisposing to fungal peritonitis be identified. We were unable to predict who would develop fungal peritonitis by analysis of nutritional, demographic, or technical factors associated with the dialysis procedure. The diagnosis of fungal peritonitis was easily established using routine blood agar culture techniques. Successful management of these patients included prompt removal of the Tenckhoff catheter and intravenous (IV) administration of amphotericin.

Amphotericin B↗

Rapid detection of group B streptococci directly from vaginal swabs.

Duplicate vaginal swabs were obtained from patients who attended obstetric or gynecologic clinics affiliated with the Magee Womens Hospital in Pittsburgh. One swab was cultured semiquantitatively on 5% sheep blood agar to detect group B streptococci (GBS). The other swab was subjected to a rapid method (25 min) for antigen detection and micronitrous acid exposure to extract the GBS antigen, followed by latex particle agglutination. A total of 464 swabs were evaluated by direct plating. Fifty-two swabs (11.2%) were found to contain GBS. Overall, the rapid method detected 21 of 52, or 40.4%, positive specimens. The sensitivity of the rapid method for identifying the most heavily colonized samples was 85.7%. This method can be used to identify maternity patients who are heavily colonized with GBS and are at high risk of delivering septic infants.

Antigens, Bacterial↗

Phrenic nerve stimulation in normal subjects and in patients with diaphragmatic weakness.

Phrenic nerve stimulation is often considered to be difficult and unreliable. The time taken for the phrenic nerves to be located and adequately stimulated was measured in 110 subjects, aged 21-89 years, 26 of whom had diaphragmatic weakness; and phrenic nerve conduction time was recorded in 76 of these individuals. Each phrenic nerve was stimulated transcutaneously in the neck with square wave impulses 0.1 ms in duration at 1 Hz and 80-160 volts while diaphragmatic muscle action potentials were recorded with surface electrodes. The time taken to locate either phrenic nerve ranged from two seconds to 22 minutes (median 10s). Both nerves were located in 83 of the 84 control subjects (99%) and in 21 of the 26 patients with diaphragmatic weakness (81%). Mean (SD) phrenic nerve conduction time in the control subjects was 6.94 (0.77) ms on the right and 6.61 (0.77) ms on the left. A weak relationship was found between conduction time and the subjects' age and height. Four out of 24 patients with diaphragmatic weakness had a prolonged phrenic nerve conduction time. Transcutaneous stimulation of the phrenic nerves was not a time consuming procedure, and it was well tolerated, reproducible, and successful in 95% of subjects.

Adult↗

A phase II trial of cyclophosphamide, etoposide, and cisplatin with combined chest and brain radiotherapy in limited small-cell lung cancer: a Cancer and Leukemia Group B Study.

Limited-extent small-cell lung carcinoma (SCLC) remains a therapeutic problem with little improvement in complete response (CR) rates and long-term survival in the past 5 years. From June 1984 through January 1985, 56 patients with limited-extent SCLC were enrolled in a Cancer and Leukemia Group B (CALGB) phase II study using five cycles of cyclophosphamide (500 mg/m2 intravenously [IV] day 1), etoposide (80 mg/m2 IV days 1 to 3), and cisplatin (33 mg/m2 IV days 1 to 3) administered at 3-week intervals (CEP), with radiation therapy (50 Gy to chest and 30 Gy to brain) administered concomitant with cycles 4 and 5, followed by three cycles of cyclophosphamide (500 mg/m2 IV day 1), etoposide (80 mg/m2 IV days 1 to 3), and doxorubicin (50 mg/m2 IV day 1). Of 49 patients evaluable for response, the overall response rate was 88%, with 57% CRs. The median overall survival was 14 months; the median duration of CR was 10 months, and nine CRs remain disease free at a median follow-up of 23 months. Toxicity was significant: 56% patients experienced WBC less than 1,000 microL, 32% platelets less than 25,000 microL and 10% hemoglobin less than 7 g/dL. There was one treatment-related septic death. These results are as good as the best previous CALGB study of SCLC, despite a reduction in duration of treatment from 18 to 5 months. We are currently using a variant of this multimodality treatment approach as our standard management for patients with limited-extent SCLC.

Adult↗

Carboplatin or iproplatin in advanced non-small cell lung cancer: a Cancer and Leukemia Group B Study.

The effect of the cisplatin analogs carboplatin (CBDCA) or iproplatin (CHIP) was evaluated in patients with extensive non-small cell lung cancer. The randomized phase II design was used to achieve balance between patient groups and comparison of response rates was not a primary objective of the study. CBDCA (400 mg/m2 iv) or CHIP (270 mg/m2 iv) was administered every 4 weeks until relapse of disease. Overall, 11 of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: 1%-13%) responded to CHIP. There were two complete responses to CHIP and none to CBDCA. The most frequent severe or life-threatening toxic effects were thrombocytopenia and leukopenia. Median survival for patients receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small cell lung cancer is warranted.

Adult↗