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Biomedical subjects

M Knight

Publications and source records attributed to M Knight.

At least 73 records · Page 4Linked to original sources
PubMed1982

The antiviral action of interferon.

On interferon treatment cells develop an antiviral state. This requires time and RNA and protein synthesis. At least six polypeptides and two enzymes have been reported to be synthesized in increased amounts in response to interferon and a multiplicity of effects have been attributed to it. Interferon has been reported to inhibit virus growth at the level of the uncoating of the virus, virus RNA and protein synthesis and virus maturation. This has led to the acceptance of a multisite model for interferon action. The evidence for this and for the role of two known interferon-mediated enzymes, the 2-5A synthetase and protein kinase, are reviewed.

Adenosine Monophosphate↗
PubMed1982

Control of the ppp(a2'p)nA system in HeLa cells. Effects of interferon and virus infection.

HeLa cells have an unusually high level of ppp(A2'p)nA synthetase (n = 2 to greater than or equal to 4) even in the absence of interferon treatment. In accord with this ppp(A2'p)nA and ppp(A2'p)nA-mediated ribosomal RNA cleavage occur naturally in response to encephalomyocarditis virus infection in control as well as in interferon-treated cells. Despite this, in the absence of interferon treatment, encephalomyocarditis virus grows well in these cells. A possible explanation for this paradox is that the ppp(A2'p)nA dependent RNase is lost or inactivated at later times post-infection in control but not in interferon-treated cells. It appears, therefore, to be the prevention by interferon of the virus-mediated inhibition of the ppp(A2'p)n-dependent nuclease rather than the absolute level or induction of the ppp(A2'p)nA synthetase which is crucial for the activity of the ppp(A2'p)nA system in HeLa cells. These results provide evidence for a further level of control in the ppp(A2'p)nA system and show that limited ppp(A2'p)nA-mediated ribosomal RNA cleavage alone is not sufficient to cause an inhibition of virus growth.

Adenine Nucleotides↗
PubMed1981

The 2-5A (pppA2'p5'A2'p5'A) and protein kinase systems in interferon-treated and control cells.

With respect to interferon action in general: multisite models and analogies with hormone action are in vogue. More particularly, concerning the 2-5A system, the structure of 2-5A has been confirmed. We know that in the cell-free system and intact cell it is unstable and in the absence of a regenerating system transiently activates a nuclease. This nuclease shows some specificity; preferentially cleaving RNA on the 3'-side of UN doublets (UA and UU are preferred). When introduced into the intact cell 2-5A can inhibit protein and DNA synthesis and virus growth. In addition, both 2-5A and core occur naturally in amounts sufficient for them to play a part in the antiviral and antigrowth activities of interferon. Finally, it is possible that the 2-5A system may have a significance beyond its role in interferon action in the control of cell growth or development.

Adenine Nucleotides↗
PubMed1980

Radioimmune, radiobinding and HPLC analysis of 2-5A and related oligonucleotides from intact cells.

The enzyme (2-5A synthetase) which synthesizes ppp(A2'p)nA where n=2 to 4 (collectively referred to as 2-5A) is widely distributed in a variety of cells and tissues in amounts which increase response to interferon and vary with growth and hormone status. 2-5A activates a nuclease which inhibits protein synthesis. The non-phosphorylated 'core' of 2-5A ((A2'p)nA, n=2 to 4) can inhibit DNA synthesis and cell growth. Here we describe convenient and sensitive radioimmune (RI) and radiobinding (RB) assays for core and 2-5A. In combination with more satisfactory high performance liquid chromatography (HPCL) methods using reverse-phase C18 columns, these assays have been used to detect core and 2-5A in crude extracts from interferon-treated cells. The novel 2-5A synthetase products NAD2'p5' A2'p5'A and A5'p45'A2'p5'A2'p5'A (ref. 13), which can also be detected using the RB assay, were not found in significant amounts. The natural occurrence of core has not been described previously.

2',5'-Oligoadenylate Synthetase↗
PubMed1979

Enkephalin generating activity of rat brain endopeptidases.

An amphiphilic substrate was used as the basis of a specific assay for peptidases which generate the opioid peptide methionine enkephalin. The substrate [Homoarg-14C]Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Homoarg is prepared by guanidination of the lysine analogue (which is beta-lipotropin 61-69) with O-methyl-[14C]isourea and is quantitatively adsorbed to dextrancoated charcoal. The COOH-terminal tetrapeptide is not adsorbed and, since it carries the radioactive label, is easily assayed in the charcoal-free supernatant fluid. Two enzyme activities have been identified in rat brain which specifically convert the amphiphilic substrate to enkephalin and the resulting tetrapeptide tail. These activities are soluble and particulate, respectively, and differ in regional distribution within the brain, in their inhibition by other peptides and in Km. Based upon these characteristics, it seems likely that the soluble activity is not primarily involved in the biosynthesis of enkephalin. It does seem possible, however, that the particulate activity which we describe may play a role in opioid peptide synthesis from larger precursors.

Animals↗
PubMed1978

Metabolic regulation in Pseudomonas oxalaticus OX1. Enzyme and coenzyme concentration changes during substrate transition experiments.

Metabolic control associated with diauxic growth of Pseudomonas oxalaticus in batch cultures on mixtures of formate and oxalate was investigated by measuring intracellular enzyme and coenzyme concentrations and QO2 values during transition experiments from oxalate to formate and vice versa. In transition from oxalate to formate oxalyl-CoA reductase concentration declined after the exhaustion of oxalate and ribulose-1,5-diphosphate carboxylase and 14CO2 fixation appeared upon addition of formate. In the reciprocal transition, ribulose-1,5-diphosphate carboxylase and 14CO2 fixation rate declined sharply after formate exhaustion, and oxalyl-CoA reductase appeared only after addition of oxalate. The intracellular NAD and NADP concentrations measured in the same experiments are reported. At substrate exhaustion the proportion of NAD in the reduced form fell from 15-20% to 2%. On addition of formate to an oxalate-starved culture there was an immediate increase in the proportion of NADH to 50%; such an increase was not observed in the reverse experiment.

Aldehyde Oxidoreductases↗
PubMed1978

Combination chemotherapy and radiation therapy of undifferentiated small cell bronchogenic carcinoma.

We reviewed 76 cases of small cell bronchogenic carcinoma seen at the University of South Florida Medical Center. One third of the 55 patients who have subsequently died did so within one month of diagnosis. Thirty-five patients were treated with cyclophosphamide, adriamycin, vincristine, and radiation therapy including prophylactic cranial irradiation. Of these 35 patients, 40% demonstrated a complete remission for a total objective response rate of 63%. The projected median survival of patients referred for study is 14 months. Improved survival was found in patients less than 60 years of age, with limited disease, who responded to treatment and in whom there were no violations of protocol. Patients treated with combination therapy appear to survive longer than untreated patients and those treated with radiation therapy alone. Toxicity was tolerable and there were no deaths related to treatment. Small cell bronchogenic carcinoma is a rapidly progressive systemic disease responsive to multimodality therapy with long-term survival in some patients.

Adult↗
PubMed1977

Volvulus of the sigmoid colon.

The clinical presentation and treatment of 31 consecutive patients with sigmoid volvulus are reviewed. Nearly half of these patients had a history of mental illness and one-third of all patients were chronically constipated. The main clinical features of abdominal pain and gross abdominal distension had been present for an average of 8 days before presentation of the patient to hospital. The clinical diagnosis of sigmoid volvulus was not difficult but the presence of non-viable bowel was more difficult to establish. A silent abdomen was the most valuable indication of the presence of gangrenous bowel. Conservative measures, including sigmoidoscopy and therapeutic barium enema, successfully reduced the volvulus in half of the cases so treated. In those patients undergoing surgery the procedure associated with the lowest mortality was sigmoid resection with end-to-end anastomosis. The overall mortality was 35%.

Adult↗