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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 415 records · Page 23Linked to original sources

A new Streptococcus group A M-29 variant isolated during a suspected common-source epidemic.

In the summer of 1988, a large epidemic of acute pharyngitis occurred in an Israeli military base. The clinical features were those of acute pharyngitis. The epidemic curve was characteristic of a common-source outbreak, possibly food-borne. Throat swabs from a sample of cases were positive for group A streptococci. Nine isolates from the epidemic were further evaluated at the local reference laboratory and serotyping showed that all were of the same strain with a distinct M protein that is a hitherto undescribed variant of M-29. We discuss the significance of unusual strains of beta-hemolytic Streptococcus appearing in food-borne outbreaks.

Acute Disease↗

Anesthetic activity of the lipospheres bupivacaine delivery system in the rat.

The Lipospheres Bupivacaine Delivery System (bupivacaine-lipospheres) is a novel sustained-release local anesthetic preparation that has recently been made available for research purposes. This investigation compared the local anesthetic efficacy and safety of 2% bupivacaine-lipospheres, 0.5% bupivacaine plus 1:200,000 epinephrine, lipospheres plain, and physiologic saline following subcutaneous tail injection in the rat. A modified tail-flick paradigm was used to assess local anesthetic efficacy. Animals treated with 2% bupivacaine-lipospheres or 0.5% bupivacaine with epinephrine displayed significant antinociception (P < 0.05) compared to saline or lipospheres plain with 5 min of injection. Bupivacaine with epinephrine had an anesthetic duration of 30 min, whereas 2% bupivacaine-lipospheres had a duration of 3 hr. The local anesthetic blockade produced by both active solutions was completely reversible. All animals gained weight normally during the 1-wk course of the study, and there were no signs of local tissue toxicity at the injection sites. We conclude that 2% bupivacaine-lipospheres is a safe and efficacious local anesthetic preparation in this particular animal model. It possesses an onset of action that is a rapid as 0.5% bupivacaine with 1:200,000 epinephrine, and a duration that is six times longer.

Analysis of Variance↗

Cysteamine can induce duodenal ulceration in rats without depletion of immunoreactive somatostatin.

Single subcutaneous administration of cysteamine (2-aminoethanethiol, CSH) produces duodenal ulceration in rats within 24 h. Depletion of circulating and tissue somatostatin (SOM), hypergastrinemia and gastric acid hypersecretion have all been postulated as the pathophysiological response to CSH leading to ulceration. The purpose of this study was to analyze the synthesis, storage and secretion of gastrin and SOM as well as structural changes in SOM peptide after CSH treatment. Injection of 300 mg/kg (s.c.) of CSH caused macroscopic duodenal ulcers in seven out of eight rats at 24 h. Hypergastrinemia was seen within 30 min (from 23 +/- 4 to 74 +/- 20 pmol/l), and persisted for 4 h. Antral gastrin content was elevated at 30 min (2539 +/- 114 pmol/g) when compared to saline controls (1589 +/- 101 pmol/g). Plasma SOM did not change over the 24 h but antral SOM increased at 30 min (from 120 +/- 3 to 230 +/- 23 pmol/g) and remained elevated at 2 h (374 +/- 48 pmol/g) and 4 h (357 +/- 37 pmol/g). Fundic and duodenal SOM followed a similar pattern. Antral SOM mRNA was also elevated over the first 4 h (3-fold increase, P less than 0.05). HPLC analysis of antral tissue extracts revealed the presence of additional molecular forms of SOM which, however, differed from the major products of in vitro reduction with either CSH or dithiothreitol. Thus, the in vivo effect of CSH on SOM cannot be solely explained by a reductive opening of the disulphide bond. These results suggest that duodenal ulceration in rats treated with CSH is not related in a simple fashion to depletion of immunoreactive SOM. Early induction of hypergastrinemia may be important in the onset of ulceration. The value of CSH as a SOM depleting tool in gastrointestinal tissue must remain in doubt.

Animals↗

Regulation of endoplasmic reticulum stress proteins in COS cells transfected with immunoglobulin mu heavy chain cDNA.

The mechanism by which endoplasmic reticulum (ER) stress proteins are induced by the accumulation of incompletely assembled or malfolded proteins in the ER is poorly understood. The 78-kDa glucose-regulated protein (BiP), one of the ER stress proteins, has often been detected in stable complexes with these accumulated proteins. We have transfected COS cells with an immunoglobulin (Ig) mu heavy chain expression plasmid. Expressed mu-chain accumulated in the cells and formed stable complexes with BiP. As a result, the synthesis of three ER stress proteins, BiP, the 94-kDa glucose-regulated protein (GRP94/ERp99), and ERp72, was increased as were their mRNA levels. In addition, the degradation rate of BiP was increased, possibly because of its interaction with mu-chain. Cotransfection of the mu-chain plasmid with an Ig lambda light chain expression plasmid resulted in the appearance of mu-chain in the media in a covalent complex with lambda-chain. An intracellular consequence of this was a reduction in the levels of BiP.mu-chain complex, and a diminished stimulation in the synthesis of the ER stress proteins. These results suggest that the BiP.mu-chain complex in the ER may be involved in the signaling pathway for the induction of ER stress proteins and may represent one regulatory mechanism operating in differentiating B-lymphocytes.

Cell Line↗

Isolation of a cellular protein that binds to the human immunodeficiency virus Tat protein and can potentiate transactivation of the viral promoter.

The human immunodeficiency virus type 1 Tat protein is a powerful transactivator of the viral long terminal repeat (LTR). We have identified a cellular protein that strongly binds to Tat and can complement Tat transactivation in rodent cells. The cellular protein of about 36 kDa was isolated from extracts of human cells by Tat peptide-affinity chromatography and can form a complex with Tat in vitro. Tat transactivation is inefficient in rodent cells microinjected or transfected with the reporter plasmid pHIV-LTRCAT plus the Tat-expressing plasmid pCV-1. Remarkably, coinjection of purified 36-kDa protein with pHIV-LTRCAT plus pCV-1 stimulated Tat transactivation 2.7- to 4.9-fold. Taken together, our findings suggest that the 36-kDa protein may be a transcription factor or modulator that is important for efficient Tat transactivation.

3T3 Cells↗

Ventricular function during supine bicycle exercise in univentricular connection with absent right atrioventricular connection.

Fourteen patients with univentricular connection, absent right connection (tricuspid valve atresia) and normally related great arteries underwent rest and supine bicycle exercise equilibrium radionuclide blood pool studies. Ejection fraction, heart rate, systemic blood pressure and oxygen saturation (ear oximetry) were measured. There were 6 male and 8 female patients. Mean age +/- standard error of the mean was 14.5 +/- 1.1 years (range 6.3 to 21.1). Eight patients (group 1) had systemic to pulmonary shunts placed as palliation 8.2 +/- 2.2 years before study and 6 patients (group II) had caval to pulmonary shunts placed 11.8 +/- 1.6 years previously. Ejection fraction at rest was 54 +/- 2% and an abnormal response to exercise (failure of ejection fraction to increase greater than or equal to 5% from rest to peak exercise) was found in 9 of 14 patients. When analyzed separately, ejection fraction at rest in group I was higher than in group II; however, this difference disappeared at peak exercise. There was a significant negative correlation between ejection fraction at peak exercise and the interval since palliative surgery, although it was not apparent at rest. These data suggest that ventricular function is compromised during exercise and that abnormal performance is influenced by long-standing volume overload. Importantly, this abnormal state is concealed at rest and the choice of palliative shunting procedure appears to have little effect on normalizing pump performance.

Adolescent↗

Reduction of transmission of shigellosis by control of houseflies (Musca domestica)

The effect of control of houseflies on the incidence of diarrhoea and shigellosis was evaluated in a prospective crossover intervention study at two military field bases several kilometers apart. In early summer, 1988, intensive fly control measures (mainly bait and trap strategy) were introduced on one base, while the other served as a control. After 11 weeks, as new cohorts arrived, the intervention was abruptly discontinued in the first base and instituted in the second for the next 11 weeks. The study was repeated the next summer. Overall, fly counts were 64% lower on the bases exposed to fly control measures (p = 0.024). Concomitantly, clinic visits dropped by 42% (p = 0.146) for diarrhoeal diseases and by 85% for shigellosis (p = 0.015), as did rates of seroconversion, by 76% (p = 0.024) for antibodies to Shigella and by 57% (p = 0.006) for antibodies to enterotoxigenic Escherichia coli. The findings indicate that houseflies, acting as mechanical vectors, transmit Shigella (and possibly enterotoxigenic E coli) diarrhoeal infections.

Adolescent↗

Analysis of the retention signals of two resident luminal endoplasmic reticulum proteins by in vitro mutagenesis.

Protein disulfide isomerase (PDI, ERp59), ERp72, and ERp61 are luminal proteins of the endoplasmic reticulum (ER) that are characterized by the presence of sequences corresponding to the active site regions of PDI. Each one of these proteins possesses a different COOH-terminal tetrapeptide ER retention signal. In order to investigate what other tetrapeptide sequences could serve as retention signals and to determine to what extent the function of the retention signal is modulated by the protein carrying the signal, we have constructed a set of mutants of two of these resident ER proteins, PDI and ERp72. In each of these proteins, the wild type tetrapeptide sequences were replaced by each member of the set of the 12 possible combinations consisting of (K,R,Q)-(D,E)-(D,E)-L. Analysis of the efficiency of retention of the variant proteins when each was transiently expressed in COS cells showed that the retention efficiencies vary with both the COOH-terminal sequence and with the protein that carries this sequence.

Amino Acid Sequence↗

N-(fluorenyl-9-methoxycarbonyl) amino acids, a class of antiinflammatory agents with a different mechanism of action.

Several members of a series of N-(fluorenyl-9-methoxycarbonyl) amino acids were found to possess a broad spectrum of antiinflammatory activity. The compounds were active against oxazolone dermatitis in mice and adjuvant arthritis in rats, models in which activated T lymphocytes are implicated. The compounds also inhibited T-lymphocyte activation in vitro, assessed by using the mixed lymphocyte reaction. The compounds inhibited the reversed passive Arthus reaction in rats and arachidonic acid-induced dermatitis in mice, models in which leukocyte infiltration is responsible for the inflammatory reaction. More complete evaluation was made of one compound, N-(fluorenyl-9-methoxycarbonyl)leucine (NPC 15199). On histologic examination after arachidonic acid administration, NPC 15199 was found to block recruitment of neutrophils into the inflammatory site. The compound was not a general myelotoxin. Prolonged treatment of animals did not alter bone-marrow progenitor number or the numbers of circulating white blood cells. Further, several white cell functions were not inhibited in vitro, including neutrophil respiratory burst and macrophage phagocytosis. NPC 15199 was effective in blocking antigen arthritis in rabbits and was effective in a therapeutic protocol, reversing oxazolone edema. These studies suggest that N-(fluorenyl-9-methoxycarbonyl) amino acids may be valuable therapeutic agents for inflammatory diseases.

Amino Acids↗

Solid phase extraction of oxcarbazepine and its metabolites from plasma for analysis by high performance liquid chromatography.

A rapid, sensitive and simple-to-operate high performance liquid chromatographic method for the simulataneous determination of oxcarbazepine, 10-hydroxycarbazepine and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine in plasma is described. The drug and its metabolites were extracted from plasma using commercially available reversed phase octadecylsilane bonded-silica columns (Bond Elut C18, 1 mL capacity). Chromatographic separation of oxcarbazepine and its metabolites was achieved using a mobile phase consisting of acetonitrile/methanol/water (13:25:62 by volume) at a flow rate of 1.2 mL/min in conjunction with a Waters Associates Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a LiChrospher 5 microns C18 guard column. By measuring the UV absorbance at 214 nm, plasma levels in the region of 50-100 ng/mL for the drug and its metabolites can be detected with only 100 microL of plasma. The method has been applied to pharmacokinetic studies of oxcarbazepine and its metabolites in children with epilepsy; preliminary pharmacokinetic findings in two patients at steady-state are presented.

Anticonvulsants↗

Trunk positioning accuracy in the frontal and sagittal planes.

The accuracy with which the head and spine could be positioned in the frontal and sagittal planes relative to the pelvis was measured and compared in ten healthy adult males. Subjects were tested with eyes closed, while standing with their pelvis externally restrained. The positions of markers, attached to the back of the head and over each of the T1, T6, T11, and L3 spinous processes, were measured to the nearest mm using strain-gaged flexible beam transducers. Subjects were tested for their accuracy in sensing return of the trunk to an initial neutral position under different test conditions. Results showed that positioning was 16-45% more accurate in the frontal than in the sagittal plane, although the difference did not reach statistical significance. T1 could be centered to within 7 and 10 mm in the frontal and sagittal planes, respectively. No significant differences were found between active and passive positioning accuracies. Presence of an external trunk moment did not significantly affect trunk positioning accuracy, although it systematically caused overshoot of the neutral position. Lastly, lateral trunk shifts exceeding 12 mm may be classified as abnormal in young adults.

Adolescent↗

Carboplatin and vinblastine in advanced non-small-cell lung cancer: a phase II study.

Between July 2, 1987, and August 21, 1987, Cancer and Leukemia Group B (CALGB) conducted a phase II evaluation of carboplatin (CBDCA) and vinblastine (VBL) in advanced non-small-cell lung cancer. Of the 58 patients who entered the study, 55 were eligible and produced follow-up data. Chemotherapy, which was carried out in 28-day cycles, consisted of 4 mg/m2 VBL given on days 1 and 3 and 125 mg/m2 CBDCA given on days 1-3. Partial responses were observed in 10 cases (18%), and 1 patient (2%) exhibited regression of evaluable disease. No complete responses were achieved. The overall objective response rate was 20%. The median survival was 6.1 months, and the median time to treatment failure was 3.3 months. Life-threatening (grade 4) toxicity was mainly leukopenia (20%), followed by anemia (7%), infection (4%), thrombocytopenia (2%), fever (2%), nausea and vomiting (2%), and weight loss (2%). There were two deaths due to infection. The results of this study demonstrate that the combination CBDCA/VBL is active in advanced NSCLC; however, whether this combination is more active than either CBDCA or VBL alone is unknown.

Antineoplastic Combined Chemotherapy Protocols↗

Mapping of HIV-1 Tat protein sequences required for binding to Tar RNA.

We have utilized a gel retardation assay to study the binding of chemically synthesized domains of the HIV-1 Tat protein to radiolabeled trans-activating response element (Tar) RNA. As with recombinant Tat protein, synthetic Tat specifically binds to Tar RNA and not to a defective Tar RNA or to anti-sense Tar RNA. The 6 amino acid portion of the basic region containing five arginines is sufficient to confer Tar binding to overlapping Tat protein fragments; Tat fragments that lack the basic region do not bind Tar. In addition, the basic region alone can also bind Tar RNA; however, binding of the basic region is non specific since defective Tar RNA is bound as well as wild type Tar RNA. Binding specificity for wild type Tar RNA can be conferred by the addition of a minimum of 8 random amino acids to either end of the basic region.

Amino Acid Sequence↗

Prevalence and correlates of diphtheria toxin antibodies among young adults in Israel.

The paucity of information about immunity against diphtheria of young adults in Israel prompted us to analyse sera from a random sample of 480 recruits (263 males and 217 females) aged 18-19 years. Antitoxin antibody levels were determined by means of ELISA. Of the recruits 58.1% had antibody values greater than 0.1 IU/ml; 38.5% had amounts between 0.01 and 0.1 IU/ml, which is considered low when using the ELISA method, and 3.3% had less than 0.01 IU/ml. The results of this study suggest that a booster dose of antidiphtheria vaccine should be given to adults in Israel in order to ensure adequate antibody levels.

Adolescent↗

Adjuvant therapy of colorectal cancer: an overview.

The substantial recurrence rate of colorectal cancer following potentially curative resection has fuelled the search for effective adjuvant therapy. Previous trials using 5-fluorouracil (5-FU) as a single agent or in combination chemotherapy regimens have not demonstrated meaningful benefits, an impression reflected in the results of a meta-analysis encompassing large patient numbers. Newer developments utilizing intraportal chemotherapy and the combination of 5-FU and levamisole have resulted in lower recurrence rates and improved survival in patients with colon cancer. In advanced disease, the biochemical modulation of 5-FU by Leucovorin has been shown to prolong survival in some studies. Combined chemotherapy and radiotherapy or chemotherapy alone have showed promising results in rectal cancer. These developments have now been incorporated into ongoing trials.

Antineoplastic Agents↗