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Biomedical subjects

G J Murphy

Publications and source records attributed to G J Murphy.

At least 19 recordsLinked to original sources

Physical medicine modalities and trigger point injections in the management of temporomandibular disorders and assessing treatment outcome.

Temporomandibular disorders (TMDs) are principally musculoskeletal, orthopedic, and neurologic in nature. The use of trigger point injections and physical medicine modalities has become commonplace in the management of TMDs. These modalities have a long and successful history in the management of similar disorders in other areas of the body, and it is only natural that they would be included in the management of TMD as well.

Electric Stimulation Therapy

Agonist potency at the cloned human beta-3 adrenoceptor depends on receptor expression level and nature of assay.

The cloned human beta-3 adrenoceptor was expressed in Chinese hamster ovary cells at three different levels (130, 400 and 3000 fmol/mg). The potency and intrinsic activity of a range of agonists in functional assays with these cell lines rose as a function of increasing receptor density. Operational analysis of concentration-response data allowed calculation of functional affinity and efficacy of agonists at the human beta-3 adrenoceptor. The data highlighted the low efficacy of BRL 37344 ¿(RR,SS)-(+/-)-4-[(2-(2-(3-chlorophenyl)-2-hydroxyethyl)amino)-propyl] phenoxyacetate¿ for the human beta-3 adrenoceptor, which may explain its lower potency at the human receptor despite its higher affinity relative to isoprenaline. The potency of catecholamines at the human beta-3 adrenoceptor was found to be 1 to 2 orders of magnitude higher when determined in an intact cell cAMP accumulation assay compared with a membrane-based adenylyl cyclase activation assay. The reason for this enhanced sensitivity is not clear, but the result is that the potency of the natural agonist noradrenaline in the intact cell is considerably higher than predicted either from its ligand binding affinity, or from its potency in membrane-based assays. Much smaller enhancements in sensitivity were observed for compounds of the aryloxypropanolamine class such as CGP 12177 [(+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one], with the result that the rank order of potency of such agonists at the beta-3 adrenoceptor was altered. In particular, CGP 12177 exhibited high relative potency in the cyclase assay, but low relative potency in intact cell assays. These findings highlight the importance of selecting appropriate expression levels and appropriate assay methodology when cloned receptors are used to characterize agonists.

Adenylyl Cyclases

Chondroblastoma of the acromion.

We describe a rare case of chondroblastoma of the acromion in a 29-year-old man. In addition to the radiological progression and confirmatory histological evidence of the lesion, the relevant and more unusual aspects of this tumour are discussed.

Acromion

Stents in the oesophagus.

The use of self-expanding metal stents can markedly improve the care of patients with inoperable oesophageal malignancy. The stents can be easily introduced without the need for general anaesthesia. They have fewer complications during insertion than rigid stents and fewer complications than laser therapy. With these stents lumens of up to 2.5 cm are easily obtainable. The article considers the type of patient who may be suitable for stenting, the technique of insertion, benefits and complications of their use.

Aged

Patterns of cell division revealed by transcriptional regulation of genes during the cell cycle in plants.

Transcripts from five cell cycle related genes accumulate in isolated cells dispersed throughout the actively dividing regions of plant meristems. We propose that this pattern reflects gene expression during particular phases of the cell division cycle. The high proportion of isolated cells suggests that synchrony between daughter cells is rapidly lost following mitosis. This is the first time that such a cell specific expression pattern has been described in a higher organism. Counterstaining with a DNA specific dye revealed that transcripts from three genes (two mitotic cyclins and a cdc2-like gene) accumulate during part of interphase and early mitosis whereas transcripts from a histone H4 gene are preferentially detected only in interphase cells. Double labelling for cyclin and histone H4 transcripts confirms that these genes are expressed in different cells, and therefore at different phases of the cell cycle. The results suggest that transcriptional regulation of cell cycle related genes may be important in controlling cell division in plants, and that these genes are useful markers for identifying cells at specific phases of the cell cycle within plant meristems.

Amino Acid Sequence

Recanalization using a low speed rotational device (ROTACS) in total occlusions of the femoropopliteal artery.

A low speed rotational catheter system (ROTACS) was used to recanalize total occlusions of the femoropopliteal artery in two patient groups. In Group A, previous attempts to recanalize the occlusions using standard guidewires and catheters had failed. Group B had undergone no previous attempts at recanalization. The ROTACS was successful in recanalizing 85% and 77% of occlusions in Group A and Group B, respectively. All these patients subsequently underwent technically successful balloon dilatation. One month follow-up revealed a high rate of reocclusion (45%) in Group A but no reocclusions in Group B. Comparison of the two groups therefore does not suggest that the ROTACS device is responsible for early reocclusions. We conclude that the ROTACS has a role in recanalizing total femoropopliteal artery occlusions in the small group of patients in whom conventional recanalization attempts have failed.

Arterial Occlusive Diseases

Cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil for the treatment of metastatic non-small cell lung cancer. Limited activity of an aggressive chemotherapy regimen.

We conducted a Phase II study to determine the efficacy of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil in patients with untreated non-small cell lung cancer. Patients were accrued through the Connecticut Oncology Association (COA), an organization composed of community and university oncologists. Thirteen COA oncologists enrolled 30 patients over 12 months and 26 were eligible for the final analysis. Patients received cisplatin 75 mg/m2, doxorubicin 30 mg/m2, mitomycin C 6.5 mg/m2, and 5-fluorouracil 750 mg/m2 on day 1. The treatment was repeated every 4 weeks, with mitomycin C given during the first 3 cycles and then every other cycle. There were 5 (19%) partial responses, lasting 1.3-7.3 months. The median time to progression was 10.3 months (0.3-12.5 months). Median survival was 7.5 months (0.3-34 months). The major toxicities were related to myelosuppression and there was one septic death. This study demonstrates the limited efficacy of an aggressive regimen using "active" agents in patients with advanced non-small cell lung cancer.

Adult

Correlation of beta 3-adrenoceptor-induced activation of cyclic AMP-dependent protein kinase with activation of lipolysis in rat white adipocytes.

The lipolytic action of the beta 3-adrenoceptor-selective agonist 4-[2-[(2-hydroxy-2-(3-chlorophenyl)ethyl)-amino]propyl]-phenoxyacetic acid (BRL 37344) was compared to that of isoprenaline in adipocytes derived from rat white adipose tissue. Concentration-response curves for activation of lipolysis by each agonist correlated well with the dose-response curves for activation of cAMP-dependent protein kinase (A-Kinase). Addition of propranolol at a concentration (0.1 microM) sufficient to block beta 1- and beta 2-adrenoceptors did not affect the stimulation of either parameter by BRL 37344 or isoprenaline, indicating that lipolysis was predominantly dependent on beta 3-adrenoceptor stimulation. Blockade of beta 3-adrenoceptors by 3 microM propranolol antagonized both A-Kinase activation and glycerol release. Activation of lipolysis by BRL 37344 was blocked by treatment of the cells with N-[2-p-(bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide (H89) a potent and selective isoquinolinesulphonamide inhibitor of A-Kinase activity. Taken together, these results indicate that lipolysis in rat white adipocytes is primarily controlled by beta 3-adrenoceptors, and that cyclic AMP generation alone is responsible for activation of lipolysis in this tissue.

Adenylyl Cyclases

Multiple novel promoters from the early region in the Streptomyces temperate phage phi C31 are activated during lytic development.

Evidence is presented that transcription of most of the early genes in the Streptomyces coelicolor A3(2) phage phi C31 is from a series of unusual promoters that depend on a function expressed early in the phi C31 lytic cycle. Primer extension analysis on the 5' ends of three early mRNAs, from samples prepared 10 min after induction of a thermosensitive phi C31 lysogen, showed that the 5' ends all mapped close to highly similar sequences, which are proposed to be an important part of phage-specific promoters. In a shotgun cloning experiment, a fragment containing one of these sequences strongly activated transcription of the xyIE reporter gene in plaques of a phi C31-derived promoter-probe vector. Another of the sequences was inserted into a xyIE-containing promoter-probe plasmid vector, and promoted xyIE expression only when the host was supporting the lytic cycle of phi C31. This suggested that a transcription factor needed for activity of the promoters was present only in phi C31-infected cells. Examination of published and unpublished phi C31 sequence data revealed several more sequences that closely resemble the conserved region of the characterized promoters. Most of these are found in positions close to apparent transcription start sites mapped previously by low-resolution S1 mapping. An overall consensus sequence for the conserved region suggests a general organization (though not a primary sequence) resembling that of promoters recognized in other bacteria by the sigma 54 form of RNA polymerase.

Bacteriophages

Demonstration of inhibitory guanine nucleotide regulatory protein (Gi) function in liver and hepatocyte membranes from streptozotocin-treated rats.

By using a defined plasma-membrane preparation, functional inhibition of adenylate cyclase activity by the inhibitory G-protein (Gi) was observed in liver and hepatocyte membranes from rats made diabetic by streptozotocin. These observations contrast with previous reports which have shown a defect in Gi in this diabetic animal model. These results suggest that Gi function is not impaired in the livers of streptozotocin-treated rats and that plasma-membrane preparation procedures should be clearly defined before ascribing Gi defects to a pathological state such as diabetes.

Adenylate Cyclase Toxin

Sequence analysis of WIS-2-1A, a retrotransposon-like element from wheat.

WIS-2-1A, a 8624 bp insertion in the Glu-1A-2 locus of chromosome 1A of wheat, consists of two 1755 bp long terminal repeats enclosing a 5114 bp internal region. No long open reading frames could be found, but inspection of the predicted amino acid sequence showed regions with homology to retrotransposon structures, including a methionine tRNA initiator binding site, a nucleotide binding domain, a protease, an integrase and a polymerase. DNA replication errors have resulted in frame-shifts in the protein coding region, suggesting that retrotransposition of WIS-2-1A, if it occurs, must be mediated by trans-acting factors.

Amino Acid Sequence

Temporomandibular-related pressure thresholds: a model for establishing baselines.

The use of pressure threshold measurement to quantify tender spots and trigger points in muscles is well established. Its application to the field of temporomandibular disorders, however, has been more recent and less widely published. Pressure threshold measurement may be useful to define values for dysfunctional muscles or structures so that changes in muscle condition through a course of treatment can be quantified. Normal values for many muscles in the body have been established, but studies of this type in the masticatory system are limited and have often used a fixed, pre-determined pressure cutoff, rather than measuring thresholds across a number of patients. This pilot study seeks to determine whether normal values exist for the anterior temporalis muscles, the masseter muscles, and the lateral capsules of the temporomandibular joints. Intrarater and interrater reliability in measuring thresholds was also studied with the aim of contributing toward a methodological model for further study.

Adolescent

Cultural identification in aboriginal and Torres Strait Islander AIDS education.

The emergence of the disease AIDS in the early 1980s has resulted in a unique response. Medical, sociocultural, political, sexual, moral and racial issues have all been raised. This paper examines the way in which participation of Aboriginal and Torres Strait Islander people has resulted in the culturally appropriate and distinctive approaches evident in health education materials produced in Aboriginal and Torres Strait Islander communities. Specific cultural issues relevant to AIDS education are considered, including the use of visual and narrative communication for AIDS education; the significance of the specific concepts related to communication on sexual issues; perceptions of AIDS as alien and genocidal; the use of the Dreaming in AIDS educational resources; and implications for AIDS education.

Acquired Immunodeficiency Syndrome

The origin of matrix metalloproteinases and their familial relationships.

New computer comparisons of the sequences of mammalian matrix metalloproteinases have established for the first time strong links with bacterial metalloproteinases. We also propose that there are five groups in the family of matrix metalloproteinases, although only three are as yet well-characterized as proteins, and discuss their origin and relationships with other zinc containing proteases.

Amino Acid Sequence

A novel proline-rich protein from wheat.

A cDNA (WPRP1) encoding a wheat proline-rich protein has been isolated and sequenced. The amino acid composition shows 45% proline, with high levels of methionine, lysine and glutamic acid. The derived 378 residue amino acid sequence has a highly repetitive structure which is unlike those of other proline-rich proteins. The WPRP1 cDNA clone was used to determine the copy number and chromosomal location of the WPRP1 gene by restriction fragment length polymorphism analysis of wheat inbred lines. Although WPRP1 is encoded by a single-copy gene it is also a representative of a larger family of related sequences. RNA gel blot analysis showed that expression of WPRP1 is highest in rapidly growing tissue which together with its amino acid composition suggests a structural role for the encoded protein.

Amino Acid Sequence

Evaluation of inhibitory guanine nucleotide regulatory protein Gi function in hepatocyte and liver membranes from obese Zucker (fa/fa) rats and their lean (Fa/?) littermates.

Previous studies have shown that hepatocyte and liver membranes from insulin resistant animals exhibit an impairment of inhibitory guanine nucleotide binding regulatory protein, Gi function, such that a Gi defect may contribute towards the diabetic syndrome. In the current studies, it is shown that the demonstration of Gi activity in liver and hepatocyte membranes is dependent critically on the membrane preparation technique. A technique is defined that allows functional Gi activity to be demonstrated in liver and hepatocyte membranes from both lean (Fa/?) and obese (fa/fa) Zucker rats. Consequently, previous reports on the loss of Gi function in insulin resistant states require revaluation.

Adenylyl Cyclases