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Biomedical subjects

R Reiner

Publications and source records attributed to R Reiner.

At least 19 recordsLinked to original sources

Function and subnuclear distribution of Rpp21, a protein subunit of the human ribonucleoprotein ribonuclease P.

Rpp21, a protein subunit of human nuclear ribonuclease P (RNase P) was cloned by virtue of its homology with Rpr2p, an essential subunit of Saccharomyces cerevisiae nuclear RNase P. Rpp21 is encoded by a gene that resides in the class I gene cluster of the major histocompatibility complex, is associated with highly purified RNase P, and binds precursor tRNA. Rpp21 is predominantly localized in the nucleoplasm but is also observed in nucleoli and Cajal bodies when expressed at high levels. Intron retention and splice-site selection in Rpp21 precursor mRNA regulate the intranuclear distribution of the protein products and their association with the RNase P holoenzyme. Our study reveals that dynamic nuclear structures that include nucleoli, the perinucleolar compartment and Cajal bodies are all involved in the production and assembly of human RNase P.

3T3 Cells↗

The market made them do it. Participants in the Medicare Choices project say they're nudging out the insurance middleman--and insuring their own survival. Panel discussion.

Medicare is experimenting again. This time HCFA wants to figure out ways to expand managed care options for the elderly. Under the Medicare Choices Demonstration Project, hospitals and health systems are developing and testing alternatives to standard Medicare HMOs. Dick Davidson, president of the American Hospital Association, sees these pilot programs as the precursors to provider-sponsored organizations building up a base of knowledge about what it means to manage risk. The AHA recently convened a meeting of organizations involved in the demonstration project and asked Hospitals & Health Networks executive editor Alden Solovy to lead a panel discussion on the lessons being learned.

Aged↗

Arterial oxygen desaturation in adult dental patients receiving conscious sedation.

Forty-six adults undergoing dental procedures were monitored with a pulse oximeter for hypoxemia. Thirty-six patients received various amounts and combinations of central nervous system depressant drugs (barbiturates, sedatives, and narcotics) in addition to local anesthetics to produce a state of conscious sedation. Twenty-eight patients in the latter group received supplemental oxygen. Ten subjects served as a control group and received only local anesthesia without supplemental oxygen. Continuous monitoring by pulse oximetry revealed 151 episodes of mild, 132 of moderate, and 33 of severe arterial oxygen desaturation, although clinical signs of hypoxemia were absent. Patients with a body mass index greater than 30 or those with a smoking history greater than 30 pack-years were particularly prone to arterial oxygen desaturation.

Adult↗

Correlation between structure and biological properties of cephalosporins: the discovery of ceftriaxone.

A research programme on cephalosporins was conducted in the author's laboratory with the aim of creating compounds with improved antibacterial and pharmacokinetic properties. In the first phase of this programme, great attention was paid to the study of how the structure of a 3-heterocyclic-thiomethyl side chain is capable of influencing antibiotic activity within a large series of model compounds possessing the same acyl side chain (2-thienylacetyl) as cephalothin. Several structural and physico-chemical features of the heterocyclic thiols used and the corresponding cephalosporins were correlated with in vitro and in vivo activity. As a result of these studies, the enolic 2-methyl-6-hydroxy-5-oxo-as-triazine-3-thiol was identified as the most interesting substituent, since the corresponding cephalosporin showed a valuable resistance breakthrough against several cephalothin-resistant Proteus strains. Consequently, further studies involving the use of different acyl side chains were performed. The introduction of the basic 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino-acetyl side chain finally led to ceftriaxone, which has a very long elimination half-life of 8 hours, high beta-lactamase stability and extremely high chemotherapeutic efficacy against a broad spectrum of Gram-positive and Gram-negative pathogens. Owing to these properties, ceftriaxone is the first beta-lactam antibiotic suitable for once-daily administration.

Animals↗

Ointments for the protection against organophosphate poisoning.

Ointments for the protection against poisoning of the skin by highly toxic organophosphates or organophosphate insecticides were prepared and examined for their protective effect both on guinea-pig skin in vitro and on guinea-pigs in vivo. The results of these investigations were as follows: 1. The prophylactic application of the ointments yields 20 fold reduction of the permeation rate of the toxic organophosphate compared with unprotected skin. 2. The ointments on a polyethyleneglycol basis show their best protective effect if they contain both a base and an active substance. 3. Maximum possible protection can be achieved by applying a thick layer of ointment which should be mechanically removed (by wiping with a damp cellulose tissue) from the contamination site within 30 min.

Animals↗

Proteolytic enzymes released by liver macrophages may promote hepatic injury in a rat model of hepatic damage.

Using macrophages isolated from the livers of normal rats and from rats injected intravenously with Corynebacterium parvum 6 days previously, N-acetyl-glucosaminidase (NAG) and plasminogen activator (PA) production have been measured during in vitro culture. There was a significant increase (p less than 0.02) in the supernatant activity of NAG by the C. parvum recruited macrophages 8.05 +/- 1.17 nmol product/mg protein/h as compared with normal, 3.86 +/- 0.77 nmol product/mg protein/h. There was a similar increase in cellular NAG content by recruited macrophages 412 +/- 66 nmol product/mg protein compared with 153 +/- 35 nmol product/mg protein (p less than 0.01) in normals. When macrophages of either group were exposed in vitro to endotoxin alone or a combination of endotoxin followed by latex particles, NAG values were similar to those obtained from nonexposed cells. In contrast, PA supernatant production increased significantly (p less than 0.02) on exposure to endotoxin with a corresponding reduction in cellular PA content, but the cellular PA content and supernatant release were similar for each group of cells. There was a fourfold increase in the number of macrophages isolated from the C. parvum-treated livers/g liver weight. Thus, the hepatocytes in this model of liver injury are potentially exposed to a 10-fold increase in the concentration of the acid hydrolase NAG; potentiation of cell damage by the administration of endotoxin may be mediated through the observed increase in production of secretory enzymes such as plasminogen activator. In conclusion, this study supports the hypothesis that proteolytic products released by recruited and activated macrophages may result in hepatocyte damage.

Acetylglucosaminidase↗

Ro 13-9904, a long-acting broad-spectrum cephalosporin: in vitro and in vivo studies.

Ro 13-9904, a new parenteral cephalosporin, was found to have high in vitro activity against Enterobacteriaceae and other gram-negative bacteria, including various isolates resistant to cefuroxime, cefamandole, cefoxitin, and cefazolin. It showed promising activity against Pseudomonas aeruginosa. Although inhibitory against Staphylococcus aureus at concentrations readily achievable in plasma, it was less potent against this pathogen than cefamandole, cefazolin, or cefuroxime. Isolates of Streptococcus faecalis were uniformly resistant to all the cephalosporins tested. Ro 13-9904 was more active than cefotaxime against Proteus mirabilis, Neisseria gonorrhoeae, Neisseria meningitidis, and Haemophilus influenzae, but less active against S. aureus. Ro 13-9904 was stable to various types of beta-lactamases. Its therapeutic efficacy against experimental septicemias in mice was equal to or slightly superior to that of cefotaxime and SCE-1365 when the antibiotics were administered in repeated subcutaneous doses after bacterial challenge. Cefoperazone, and particularly cefamandole nafate, cefazolin, and mezlocillin were less effective. Although structurally related to cefotaxime and SCE-1365, Ro 13-9904 was found to differ from them in one important respect, namely, in having a long duration of action; this was observed with single-dose treatment given before bacterial challenge. Its broad spectrum of activity coupled with favorable pharmacokinetic properties make Ro 13-9904 a promising compound for clinical studies.

Animals↗

Ro 13-9904/001, a novel potent and long-acting parenteral cephalosporin.

Ro 13-9904/001 is a novel parenteral cephalosporin antibiotic with potent in vitro activity against a wide range of beta-lactamase-producing and non-producing pathogens. In addition, Ro 13-9904/001 proved to possess a very long plasma half-life and, as a consequence, high prophylactic in vivo effectiveness.

Animals↗

Iron deficiency anaemia--a prospective study.

A prospective study was performed over 15 months to determine the cause of iron deficiency in adult males and postmenopausal females attending a general hospital. The laboratory computer identified all subjects with a haemoglobin less than 10.6 g/dl and a mean corpuscular volume less than 86 fl. Patients becoming anaemic after trauma or recent surgery were excluded. The iron status of each patient was assessed by serum iron studies, serum ferritin or sternal marrow aspiration. Reduced red cell indices and blood film morphology were not diagnostic of iron deficiency. Of 215 patients assessed, about half (103) were found to be iron replete. This group had a variety of disorders--malignancy, chronic inflammation, chronic renal and non-malignant haematological diseases. The other group of 104 patients satisfied criteria for iron deficiency, and 100 of these were investigated further. The cause of iron deficiency was found in all but three subjects. Inadequate dietary intake was a contributing factor in over half of the patients and 40 regularly took salicylates. Investigation defined a source of chronic gastrointestinal blood loss in most instances.

Adult↗