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Biomedical subjects

G S Johnson

Publications and source records attributed to G S Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1997

An information-intensive approach to the molecular pharmacology of cancer.

Since 1990, the National Cancer Institute (NCI) has screened more than 60,000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI50) for any single cell line is simply an index of cytotoxicity or cytostasis, but the patterns of 60 such GI50 values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460,000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.

Algorithms↗
PubMed1997

Trauma triage: a comparison of CRAMS and TRTS in a UK population.

The CRAMS scale and the Triage Revised Trauma Score (TRTS) were compared to assess their potential use as a prehospital method of activating hospital trauma teams. We studied patients from the resuscitation room of Leeds General Infirmary who had enough data recorded to allow calculation of the admission TRTS and CRAMS scale. Patients were defined as having major injury if they died in hospital, were admitted to the ICU or had an Injury Severity Score (ISS) of > 15. Each triage scale was compared by calculating multiple sensitivity/specificity pairs and plotting the results on a receiver operator (ROC) curve. The optimal cut-offs on each scale were compared directly. Ninety-seven (46 per cent) of a total of 213 patients fulfilled the study criteria for major injury. The best cut-off points were a CRAMS of < 9 and a TRTS of < 12. The TRTS was significantly more specific (0.9 versus 0.75) but at a cost of poor sensitivity (0.6 versus 0.69, not significant). The performance of both scales was similar when compared on the ROC curve. CRAMS and the TRTS were unable to identify major injuries in our sample with sensitivity and specificity adequate to support their use as a tool to activate trauma teams in the UK.

Adult↗
PubMed1997

Casein kinase 1 is tightly associated with paired-helical filaments isolated from Alzheimer's disease brain.

The protein kinase activity tightly associated with paired helical filaments (PHFs) purified from the brain tissue of individuals with Alzheimer's disease has been characterized in vitro. The activity is shown to phosphorylate casein, an exogenous substrate, with a maximal velocity of approximately 2 nmol/min/mg, suggesting it comprises a significant component of the total protein in the PHF preparation. On the basis of substrate selectivity, isoquinoline sulfonamide inhibitor selectivity, in-gel renaturation assays, and western analysis, the activity consists of closely related members of the alpha branch of the casein kinase 1 family of protein kinases. Because of its tight association with PHFs and its phosphate-directed substrate selectivity, casein kinase 1 is positioned to participate in the pathological hyperphosphorylation of tau protein that is observed in neurodegenerative diseases such as Alzheimer's disease.

Adult↗
PubMed1997

Immunochemical localization of the Batten disease (CLN3) protein in retina.

PURPOSE: Batten disease, also known as juvenile ceroid-lipofuscinosis and CLN3, is an autosomal recessively inherited disorder that results in blindness due to retinal degeneration. The CLN3 gene has been identified, but the function of the protein that this gene encodes is unknown. Experiments were conducted to determine where the CLN3 protein is localized in the mouse retina. Localization should provide a clue in evaluating potential functions of this protein. METHODS: Using oligonucleotide primers based on the reported human CLN3 cDNA sequence, the mouse cDNA nucleotide sequence was determined from products of the reverse transcriptase-polymerase chain reaction and 3' rapid amplification of cDNA ends. A synthetic 20-amino-acid peptide corresponding to an internal hydrophilic region of the predicted amino acid sequence of the mouse CLN3 protein was used to immunize rabbits. The resulting antiserum was used in immunoblot analysis of mouse retina homogenates and in electron microscopic immunocytochemical labeling of mouse retina sections. RESULTS: The peptide antibody labeled a single protein band of approximately 50 kDa on immunoblots of mouse retina homogenates. No labeling was detected with homogenates from human retinas. The antibody specifically labeled mitochondria of Müller cells and inner retinal neurons. Little labeling was observed in mitochondria of the photoreceptor cells. Mitochondria of other cell types, including the retinal pigment epithelium and choroidal cells, were not labeled. CONCLUSIONS: The retinal CLN3 protein appears to be localized almost exclusively in the mitochondria, but was detected only in certain cell types. Batten disease is characterized by massive lysosomal accumulations of a small inner mitochondrial membrane protein (subunit c of ATP synthase). The mitochondrial localization of the CLN3 protein suggests that it may play a role in the normal processing of subunit c.

Amino Acid Sequence↗
PubMed1996

Amylaceous (polyglucosan) bodies in familial cerebral atrophy of early onset.

An 8-year-old girl and her 4-year-old sister presented with psychomotor retardation during the 1st year of life. This was followed by spasticity, seizures, and in the older patient, progressive loss of faculties and death. Computed tomographic and magnetic resonance imaging scans demonstrated progressive cerebral atrophy in both patients. Postmortem examination in the older sibling showed diffuse atrophy of the supragranular layers of the cerebral cortex, atrophy and gliosis of the white matter, and accumulation of numerous amylaceous (polyglucosan) bodies within the cytoplasm of cell processes. The inclusions were closely associated with atrophy of the parenchyma. The findings suggest that this disorder is different from other childhood diseases in which amylaceous bodies accumulate within the brain.

Adipose Tissue↗
PubMed1995

The coding sequence of the bovine ferrochelatase gene.

The amino acid code and surrounding regions in the bovine ferrochelatase gene were amplified by a combination of reverse transcriptase PCR and vectorette PCR and sequenced. The bovine code was 86% homologous to the human ferrochelatase code but was altered at a position corresponding to the presumed human initiator codon.

Amino Acid Sequence↗
PubMed1995

The effect of pre-hospital administration of intravenous nalbuphine on on-scene times.

The use of intravenous nalbuphine in pre-hospital settings by paramedics has been demonstrated to be safe and effective. We assessed the effect of this additional intervention by comparing the time spent on-scene by ambulance crews treating patients with fractures of the tibia and fibula who received intravenous nalbuphine with those who had placement of an intravenous cannula alone and those who had neither cannula nor nalbuphine. The mean on-scene times were 17.1 min without cannulation, 29.9 min for cannulation without nalbuphine and 37.5 min for cannulation and administration of nalbuphine. The benefits of effective pre-hospital analgesia thus have a cost in terms of time. Continued audit of interventions and on-scene times is important to prevent inappropriate delays in pre-hospital care which may cause clinical and operational problems.

Adolescent↗
PubMed1994

Plasma von Willebrand factor antigen concentration in dogs with hypothyroidism.

Plasma von Willebrand factor antigen concentration was measured in 10 dogs with hypothyroidism, before and after administration of a replacement dose of levothyroxine for 67 +/- 12 days. Results were reported as a percentage of normal activity, with plasma pooled from clinically normal dogs given a value of 100%. Plasma von Willebrand factor antigen concentration was within reference limits in dogs with hypothyroidism (126 +/- 41%) and was significantly (P < 0.01) decreased (94 +/- 39%) after treatment with levothyroxine. Contrary to findings in some other studies, a deficiency of plasma von Willebrand factor did not appear to result from hypothyroidism.

Animals↗