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Biomedical subjects

R Nicholson

Publications and source records attributed to R Nicholson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Human and rat malignant-tumor-associated mRNAs encode stromelysin-like metalloproteinases.

Rat transin and human stromelysin 2 mRNAs, which have been associated with malignant tumors, code for potential proteins with significant sequence homology to the metalloproteinases collagenase and stromelysin. We have used an expression system that allows easy purification of these proteins after transfection of COS cells with a vector containing the corresponding cDNA. This system has allowed us to prepare transin and stromelysin 2 as active proteinases that are inhibited by inhibitors of metalloproteinases. Further analysis of these enzymes indicates that they degrade several components of the extracellular matrix including collagen types III, IV, and V and fibronectin, as well as gelatins formed from several denatured collagen types. In addition, both transin and stromelysin 2 are capable of activating procollagenase in vitro. Thus, in malignant tumors these proteinases may act, both directly and indirectly, to degrade the extracellular matrix and permit tumor invasion of neighboring tissues.

Animals↗
PubMed1988

Structure-function relationships in the collagenase family member transin.

We have developed a system for studying the proteinase activity of a collagenase family member, transin. Cos cells transfected with a vector designed to direct synthesis of a secretable fusion protein between staphylococcal protein A and transin secrete a latent proteinase, activable by 4-aminophenylmercuric acetate, which binds to IgG-Sepharose. Treatment with 4-aminophenylmercuric acetate leads to cleavage of the fusion protein and elution of the active proteinase transin. Based on results obtained with this system we propose that transin comprises an N-terminal proteinase domain and an independent C-terminal hemopexin-like domain. The latter domain is not required for binding of inhibitors or for maintenance of transin in its inactive form. The sequence PRCGVPDV is present in the proenzyme forms of collagenase family proteinases just upstream from the N termini of the active enzymes. We show that mutations within this sequence lead to transin variants with a much increased tendency to undergo spontaneous activation. Finally, we show that mutations within a region of transin having sequence similarity to the zinc-binding site of bacterial metalloproteinases inactivate the proteinase activity of transin, lending support to the notion that this region represents part of transin's active site.

Amino Acid Sequence↗
PubMed1988

cis-acting translational effects of the 5' noncoding region of c-myc mRNA.

We have previously shown that the 5' noncoding region of mouse c-myc mRNA has a negative effect on translational efficiency in a rabbit reticulocyte lysate (A. Darveau, J. Pelletier, and N. Sonenberg, Proc. Natl. Acad. Sci. USA 82:2315-2319, 1985). We wanted to localize and characterize the inhibitory translational element(s) in the mRNA and to study its effect in other in vitro and in vivo systems. Here we report that the restrictive element is confined to a 240-nucleotide sequence of the 5' noncoding region of mouse c-myc mRNA and that this sequence acts in cis to inhibit the translation of a heterologous mRNA. In addition, we report that the cis-inhibitory effect is also exhibited in microinjected Xenopus oocytes and wheat-germ extracts but not in HeLa cell extracts. Transfection of corresponding plasmid DNA constructs into several established cell lines did not produce the cis-inhibitory effect. A model to explain these results is presented.

Animals↗
PubMed1987

Predictive power of progesterone receptor status in early breast carcinoma.

Progesterone receptor status (PgR) and oestrogen receptor status (ER) were examined in 332 women with stage I-II breast carcinoma treated at a single centre either by simple mastectomy with (n = 283) or without (n = 6) axillary clearance, or by segmental mastectomy with (n = 18) or without (n = 25) axillary clearance and radiotherapy; median follow-up time was 40 (range 10-60) months. Neither the concentration nor the presence of PgR related to either disease-free interval or survival. However both the presence and the concentration of ER were found to be associated with a longer disease-free interval amongst patients with stage II tumours (P less than 0.01). From this study it appears that progesterone receptor status does not predict outcome in early breast carcinoma.

Adult↗
PubMed1987

Expression of reovirus type 3 (Dearing) sigma 1 and sigma s polypeptides in Escherichia coli.

The reovirus S1 gene codes for two polypeptides: sigma 1 and sigma s. In order to characterize the structure and function of the sigma 1 polypeptide, we have expressed the sigma 1 protein in Escherichia coli. The S1 gene from mammalian reovirus type 3 (Dearing strain) and the variant K strain were subcloned into an expression vector containing the tac (trp-lac) promoter designed to express foreign gene products in E. coli efficiently. The hybrid plasmids, upon induction with isopropyl-beta-D-thiogalactopyranoside, expressed two polypeptides that were detected by [35S]methionine labelling. One of the induced proteins had a relative molecular mass (Mr) of approx. 46,000 and corresponded to sigma 1, as shown by immunoprecipitation with goat anti-reovirus antibody and a monoclonal antibody against sigma 1. The second induced protein had a Mr of approx. 12,000 and was very similar to sigma s as judged by comparative tryptic peptide map analysis. Protein sigma 1 produced in E. coli was shown to be functional as judged from its ability to bind to mouse L fibroblasts.

Animals↗
PubMed1986

Chronic suppurative otitis media in the Solomon Islands: a prospective, microbiological, audiometric and therapeutic survey.

Chronic suppurative otitis media affected 3.8% of 3500 Solomon Island children under 15 years (and 6.1% under 5 years) and was the sole cause of conductive hearing loss recorded in 265 children tested audiometrically. It was characterised by early onset (65% under 18 months) male preponderance and large central tubotympanic perforations. Measles, respiratory infections, swimming and malnutrition were identified as aetiological factors amenable to intervention. Proteus and pseudomonas were the principle aerobes isolated from ear pus and gentamicin the only antibiotic tested to be effective against them. However although a prospective therapeutic trial demonstrated a significantly improved outcome after aural toilet, no additional benefit was imparted by concurrent ototopical boric acid or aminoglycoside solution or oral antianaerobic clindamycin. Parental tuition in aural cleaning, avoidance of ear water entry, nose blowing and breathing will yield a good result in up to 60% of children in half of whom tympanic healing occurred.

Adolescent↗
PubMed1986

Influence of HbS levels upon the hematological and clinical characteristics of sickle cell trait.

The variable concentration of HbS in individuals with sickle cell trait led us to study the relationship between HbS level and selected vascular events in 355 hospitalized black men with sickle cell trait. There were significant differences in hemoglobin concentration and mean corpuscular volume found in four groups divided by their HbS level, the lowest proportion of HbS (less than 30%) being associated with the lowest hemoglobin concentration (12.6 g/dl) and MCV (77 fl). The percent HbS did not influence the incidence of pulmonary embolism, thrombophlebitis, myocardial infarction, cerebrovascular accident, or idiopathic hematuria. Our results suggest that HbS level does not influence vascular disease, and while certain hematological alterations occur, they are very unlikely to have any clinical significance. Regardless of the proportion of HbS, sickle cell trait in black men is benign.

Anemia, Sickle Cell↗
PubMed1985

Ethics and politics.

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Academies and Institutes↗
PubMed1985

Radioaerosol ventilation imaging in ventilator-dependent patients. Technical considerations.

The differentiation of pulmonary embolism (PE) from regional ventilatory abnormalities accompanied by reduced perfusion requires contemporary perfusion and ventilation studies. Distinguishing these conditions in ventilator-dependent patients is aided by administering a Tc-99m aerosol to characterize regional ventilation, and by performing a conventional Tc-99m MAA perfusion study. The technique uses a simple "in-house" constructed apparatus. Simple photographic techniques suffice, but computer subtraction of perfusion from the combined perfusion-ventilation image renders interpretation easier if aerosol administration follows perfusion imaging. Multiple defects can be examined in a single study. Excluding normal or near-normal perfusion studies, PE was thought to be present in eight of 16 patients after perfusion imaging alone, but in only one of eight after added aerosol imaging. Angiography confirmed the diagnosis in that patient. Of the eight patients who had abnormal perfusion but were thought unlikely to have PE from the perfusion study alone, two had normal ventilation, and subsequently were shown to have PE by angiography. Because angiography was only performed on patients who were thought to have a high probability of PE on sequential perfusion-ventilation imaging, the true incidence of PE may have been higher. Aerosol ventilation imaging is a useful adjunct to perfusion imaging in patients on ventilators. It requires an efficient delivery system, particularly if aerosol administration follows perfusion imaging, as it does in this study. The major disadvantage of aerosol imaging compared to a gas in intubated patients is the significant bronchial deposition due to retained mucus secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1984

Clinical competencies of baccalaureate students.

Clinical Competencies of new graduates from baccalaureate programs have periodically been criticized by employers of new graduates. In an effort to understand the levels of clinical preparation for new baccalaureate graduates, three hypotheses dealing with the cognitive, affective, and psychomotor domains were tested. A review of the literature reveals that most exploration and work has been done relative to the cognitive domain. Sixty-four NLN accredited baccalaureate programs responded to a request that they provide all of the clinical objectives used in their program. Findings revealed that there were clinical evaluation criteria written at all levels of the three domains; however, most schools did not have objectives at each of the levels of the three domains. A disproportionately large number of clinical objectives are written at the cognitive domain. The study raises the question as to the abilities of students to be clinically proficient upon graduation when there are relatively few evaluation criteria written in the psychomotor domain.

Affect↗
PubMed1982

Psychological and social evaluation in cases of deliberate self-poisoning seen in an accident department.

The outcome in 115 consecutive patients with mild self-poisoning seen by junior medical staff and discharged from the accident department was compared with that of 98 similar patients admitted to the medical wards. Psychiatrists saw only four patients in the accident department and 25 admissions. In making their assessments the junior medical staff considered psychosocial factors as well as the patients' physical condition. Most patients recommended for further care, and discharged from the accident department, subsequently received it. Repetition rates were similar in the two groups and there had been no suicides when patients were followed up at one year. It is feasible for junior staff in an accident department to decide whether patients with self-poisoning need admission or may be discharged with or without subsequent referral for psychiatric or social work help.

Emergency Service, Hospital↗
PubMed1982

Single copy DNA homology in sea stars.

The sequence homology in the single copy DNA of sea stars has been measured. Labeled single copy DNA from Pisaster ochraceus was reannealed with excess genomic DNA from P. brevispinus, Evasterias troschelii, Pycnopodia helianthoides, Solaster stimpsoni, and Dermasterias imbricata. Reassociation reactions were performed under two criteria of salt and temperature. The extent of reassociation and thermal denaturation characteristics of hybrid single copy DNA molecules follow classical taxonomic lines. P. brevispinus DNA contains essentially all of the sequences present in P. ochraceus single copy tracer while Evasterias and Pycnopodia DNAs contain 52% and 46% of such sequences respectively. Reciprocal reassociation reactions with labeled Evasterias single copy DNA confirm the amount and fidelity of the sequence homology. There is a small definite reaction of uncertain homology between P. ochraceus single copy DNA and Solaster or Dermasterias DNA. Similarly Solaster DNA contains sequences homologous to approximately 18% of Dermasterias unique DNA. The thermal denaturation temperatures of heteroduplexes indicate that the genera Pisaster and Evasterias diverged shortly after the divergence of the subfamilies Pycnopodiinae and Asteriinae. The two Pisaster species diverged more recently, probably in the most recent quarter of the interval since the separation of the genera Pisaster and Evasterias.

Animals↗
PubMed1976

GPC diesterase activity in human endometrial secretion. (Its variations under the action of estrogens, clomiphene citrate, D-norgestrel (post-coital and low dose) and intrauterine device (IUD).)

Diesterase activity was studied in human uterine secretions of normal women and in those under treatment for sterility or contraception. Endometrial secretions were obtained from 78 patients and the material divided into four groups: normal women, under different estrogens; with D-Norgestrel treatment (daily and post-coital) and patients with IUD Lippes D. The mean concentration of free choline delivered by the GPC diesterase in the normal group was 777 +/- 128 mug/ml (SD 286). Under hormonal treatment an increase of diesterase activity was observed. D-Norgestrel post-coital produced a fall of the enzymatic activity between 180 to 420 minutes. The uninterrupted use of D-Norgestrel (30 gammas daily) produced a loss of diesterase activity in 80% of cases studied. The use of IUD (Lippes D) did not modify the enzymatic activity in this group.

Clomiphene↗