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Biomedical subjects

K Scott

Publications and source records attributed to K Scott.

At least 19 recordsLinked to original sources

Analysis of grape ESTs: global gene expression patterns in leaf and berry.

Analysis of 2479 ESTs from Vitis vinifera berry tissue and 2438 from leaf revealed that 1% of the ESTs match to known Vitis proteins, 72% to plant proteins, 11% to non-plant, and 16% had no match (P[N]>0.5). The levels of redundancy were similar in the leaf and berry libraries. Only 12% of the genes matched by the ESTs were common to both libraries indicating marked differences in the genes expressed in the two tissues. The abundance of transcripts with predicted cellular roles in leaf and berry were estimated by classifying the primary BLAST matches to known proteins (score >80) into functional categories. Thirty-six percent of the leaf transcripts were involved in photosynthesis, compared to 3% in the berry. This is a much higher proportion of transcripts involved with a function limited to specialized cells, than was found when transcripts of 33 human tissues were compared using a similar approach, suggesting plant cells may involve their cellular machinery to a greater extent in specialized activities than animal cells. Relatively enhanced expression of specific transcription factors, and genes involved in defense, detoxification, stress response, proteolysis, trafficing, and signal transduction, suggests berry tissue is actively engaged in responding to environmental stimuli.

Journal Article↗

Impaired cued and contextual memory in NPAS2-deficient mice.

Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain. Targeted insertion of a beta-galactosidase reporter gene (lacZ) resulted in the production of an NPAS2-lacZ fusion protein and an altered form of NPAS2 lacking the bHLH domain. The neuroanatomical expression pattern of NPAS2-lacZ was temporally and spatially coincident with formation of the mature frontal association/limbic forebrain pathway. NPAS2-deficient mice were subjected to a series of behavioral tests and were found to exhibit deficits in the long-term memory arm of the cued and contextual fear task. Thus, NPAS2 may serve a dedicated regulatory role in the acquisition of specific types of memory.

Animals↗

The ryanodine receptor is essential for larval development in Drosophila melanogaster.

We have investigated the role of the ryanodine receptor in Drosophila development by using pharmacological and genetic approaches. We identified a P element insertion in the Drosophila ryanodine receptor gene, Ryanodine receptor 44F (Ryr), and used it to generate the hypomorphic allele Ryr(16). An examination of hypodermal, visceral, and circulatory muscle showed that, in each case, muscle contraction was impaired in Ryr(16) larvae. Treatment with the drug ryanodine, a highly specific modulator of ryanodine receptor channel activity, also inhibited muscle function, and, at high levels, completely blocked hypodermal muscle contraction. These results suggest that the ryanodine receptor is required for proper muscle function and may be essential for excitation-contraction coupling in larval body wall muscles. Nonmuscle roles of Ryr were also investigated. Ryanodine-sensitive Ca(2+) stores had previously been implicated in phototransduction; to address this, we generated Ryr(16) mutant clones in the adult eye and performed whole-cell, patch-clamp recordings on dissociated ommatidia. Our results do not support a role for Ryr in normal light responses.

Alleles↗

Long-term cyclophosphamide treatment for recurrent type I membranoproliferative glomerulonephritis after transplantation.

The incidence of recurrent type I membranoproliferative glomerulonephritis (MPGN) after renal transplant is approximately 30%, and the rate of graft loss due to recurrent MPGN type I is higher than 50%. The treatment of this disease has not been defined. We report a case of recurrent MPGN type diagnosed 4 months after a cadaveric renal transplantation. The patient was treated with cyclophosphamide and was able to maintain her graft function. Cyclophosphamide was interrupted three times during the course. Each time her renal function deteriorated and her serum albumin decreased. The patient currently has a functional renal graft 3 years after transplantation while receiving low-dose therapy with cyclophosphamide. We suggest treating recurrent type I MPGN with cyclophosphamide while continuing the calcineurin inhibitor and prednisone.

Aged↗

Assessment of patients with facial fractures.

One of the most demanding aspects of emergency medicine is the management of patients who have suffered facial trauma. The diagnosis and initial management of patients who have sustained traumatic facial injuries are discussed. The fundamentals required to assess patients with fractures of the facial skeleton and to make appropriate referrals are provided.

Emergency Service, Hospital↗

Activity of cecropin P1 and FA-LL-37 against urogenital microflora.

Two mammalian antimicrobial peptides, FA-LL-37 and cecropin P1, were tested for activity against six uropathogens and five Lactobacillus strains by broth microdilution assay. Both peptides inhibited Escherichia coli at 25 microM (FA-LL-39), and 1.56 microM (cecropin P1), Pseudomonas aeruginosa (12.5 microM, and 25 microM), and Klebsiella pneumoniae, (50 microM, and 1.56 microM), but not Enterococcus faecalis and Staphylococcus epidermidis. FA-LL-37 acted bacteriocidally against E. coli and bacteriostatically against the other two Gram-negative organisms. Cecropin P1 was bacteriocidal to all susceptible bacteria. Lactobacilli were resistant to both peptides, with the exception of poultry isolate Lactobacillus fermentum B-54, which was susceptible to FA-LL-37 at 100 microM. The differential activities of these peptides toward Gram-negative uropathogens versus urogenital lactobacilli demonstrate their potential as a topical treatment for urinary tract infections. In addition, production of such peptides in vivo could be a natural mechanism to aid in the maintenance of the lactobacilli-dominated urogenital flora at the expense of pathogens.

Amino Acid Sequence↗

Variation in the frequency of Epstein-Barr virus-associated Hodgkin's disease with age.

A number of studies in developed countries have reported variation in the frequency of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) with age. A 'three disease' model for HD that incorporates the EBV association, histological subtype of HD and age has recently been proposed. In this model, Hodgkin's disease of childhood and older adults is commonly EBV-associated and of mixed cellularity type, whereas young adult HD is generally not EBV-associated and is usually characterised by nodular sclerosis disease. A case series of HD diagnosed in the West Midlands between 1981 and 1997, inclusive, was used to investigate the applicability of the 'three disease' model. In situ hybridisation for the EBV early RNAs (EBERs) was used to determine the presence of EBV in the malignant Hodgkin/Reed-Sternberg cells. In contrast to the 'three disease' model, nodular sclerosis was the predominant subtype in each of the age groups within the case series. In addition, overall there was little variation in EBV-positive rates across the age ranges examined. However, when females were analysed separately, older women (45+ years) were significantly more likely to have EBV-positive disease than their younger counterparts (<45 years). In summary our results do not generally support the 'three disease' model.

Adolescent↗

Maintaining carotid flow by shunting during carotid endarterectomy diminishes the inflammatory response mediating ischaemic brain injury.

OBJECTIVES: to assess whether shunting during carotid reconstruction affects the release of inflammatory mediators from the ipsilateral hemisphere. MATERIALS AND METHODS: a catheter was placed in the ipsilateral jugular bulb during carotid endarterectomy (CEA) in 20 patients. Eight patients with ICBP (internal carotid backpressure) <40 mmHg received a shunt during CEA and 12 patients with ICBP >40 mmHg were operated upon without a shunt. Four patients with a carotid body tumour were used as controls. Blood was taken from the catheter as well as from the radial artery; before clamping, 5, 15, 30 min after clamping and 5 min after declamping. The oxygen extraction (AVO(2)) was calculated. Plasma concentrations of interleukin-1beta (IL-1beta), phospholipase A(2)(PLA(2)), thromboxane B(2)(TXB(2)), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and prostaglandin E(2)(PGE(2)) were measured by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: all patients had a normal postoperative course except for one patient in the no-shunt group, who suffered a stroke 1 h later due to occlusion of the endarterectomy site. The AVO(2)extraction increased during clamping in patients operated upon without a shunt (p <0.05). This increase was partly recovered to pre-clamp levels 5 min after reperfusion. The extraction remained stable in the non-shunted patients and the control group. The increased extraction in the non-shunted group correlated with increased levels of IL-1beta during clamping ( p <0.05) and reperfusion ( p <0.01). PLA(2)also increased during reperfusion in the non-shunted group ( p <0.05). An increased ratio between TXB(2)and 6-keto-PGF1alpha was noted during clamping ( p <0.05) and further increased during reperfusion. The levels of PGE(2)remained stable in both CEA groups. The PLA(2)levels, as well as TXB(2), 6-keto-PGF1alpha and PGE(2)levels, remained unchanged during the procedure in the control group. CONCLUSIONS: there is a metabolic response to carotid cross-clamping when no shunt is used. However, the clinical significance of this is unclear, since there were no intraoperative strokes.

Aged↗

Relation of Bcl-2 expression to androgen receptor, p21WAF1/CIP1, and cyclin D1 status in prostate cancer.

BACKGROUND: There is currently no effective treatment for recurrent hormone refractory carcinomas of the prostate gland. An understanding of the underlying mechanisms responsible for the progression of these lesions is likely to be important for the development of new therapeutic approaches. Recently, it has been suggested that the transition to a hormone independent state is accompanied by increased proliferation and bcl-2 gene expression, as well as by a decreased apoptotic state. AIM: To investigate the possible role of Bcl-2 and other cell cycle regulating proteins in the development of prostatic tumours. METHODS: Immunohistochemistry was used to study the relation between the expression of Bcl-2 and the androgen receptor, as well as p21WAF1/CIP1 (p21), and cyclin D1 status, in a series of 89 prostate cancer samples taken before androgen withdrawal treatment. RESULTS: Androgen receptor negative tumours expressed significantly higher amounts of Bcl-2 than those prostate carcinomas with low/medium androgen receptor values. However, in tumours expressing the highest amounts of androgen receptor, Bcl-2 expression was also high. A significant positive relation between Bcl-2 and p21 expression, as well as an inverse relation between Bcl-2 and cyclin D1 expression, was noted. Androgen receptor positive samples also expressed significantly higher amounts of cyclin D1. CONCLUSIONS: These results suggest that p21 and cyclin D1 expression in prostatic cancer might be modulated by Bcl-2 and by androgens and in turn this could be relevant to the progression of prostatic cancer.

Cyclin D1↗

Effect of Epstein-Barr virus infection on response to chemotherapy and survival in Hodgkin's disease.

We have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin's disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P =.05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P =.02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P =.18 and P =.40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.

Antineoplastic Combined Chemotherapy Protocols↗

TCR-mediated involvement of CD4+ transgenic T cells in spontaneous inflammatory bowel disease in lymphopenic mice.

Spontaneous colitis resembling ulcerative colitis developed in 3 of 10 independent TCR transgenic (Tg) mouse lines maintained under specific pathogen-free conditions. All three susceptible lines were CD4 lymphopenic, whereas resistant lines had normal numbers of CD4+ T cells. Thus, cytochrome c-specific 5C.C7 TCR Tg mice developed colitis only when crossed onto a SCID- or Rag-1-deficient background. A second line of lymphopenic cytochrome c-specific Tg mice bearing the AND TCR also developed colitis. In both cases, CD4+ T cells expressing the Tg-encoded TCR were preferentially activated in inflamed colons compared with lymph nodes or spleens. In contrast, Tg+CD4+ T cells remained quiescent in both inflamed and unaffected colons in another line of susceptible Tg mice carrying a TCR specific for myelin basic protein, suggesting a fortuitous cross-reactivity of the IEk-restricted cytochrome c-reactive AND and 5C.C7 TCRs with an Ag present in the gut. The percentage of CD4+ T cells expressing only endogenous TCR alpha-chains was increased consistently in inflamed colons in AND as well as 5C.C7 Rag-1-/- TCR Tg mice, suggesting that polyclonal CD4+ T cells were also involved in the pathogenesis of spontaneous colitis. Moreover, our data indicate that some alpha-chain rearrangement was still occurring in TCR Tg mice on a Rag-1-/- background, since activated CD4+ T cells expressing endogenously rearranged alpha-chains paired with the Tg-encoded beta-chain were detected consistently in the colons of such mice.

Adoptive Transfer↗

Dealing with a bleeding nuisance: a study of haemophilia care in New Zealand.

AIM: To describe the social and demographic characteristics of people with haemophilia in New Zealand and to identify key issues in their treatment. METHODS: The research (1994-6) used a combination of quantitative and qualitative methods, including key person interviews and focus groups, a national survey (n=193), interviews (80), participant observation and consultative report writing (30 participant-consultants). RESULTS: The study population was mainly (95%) male, somewhat younger than the general New Zealand population, and was 90% Caucasian but otherwise conformed closely to the socio-demographic profile of the general population. Participants clustered towards the severe end of the condition of haemophilia. There was great variation between participants in incidence of bleeds. Legs and arms were most commonly affected. The majority (61%) of bleeds were treated within six hours of detection. Despite considerable advances and an emphasis on the provision of adequate and prompt treatment, there is still much room for improvement to obviate problems such as joint damage, pain and the need for surgery. CONCLUSIONS: People with haemophilia and haemophilia health service providers struggle to achieve optimal care.

Adolescent↗

Lipase-catalyzed fractionation of conjugated linoleic acid isomers.

The abilities of lipases produced by the fungus Geotrichum candidum to selectively fractionate mixtures of conjugated linoleic acid (CLA) isomers during esterification of mixed CLA free fatty acids and during hydrolysis of mixed CLA methyl esters were examined. The enzymes were highly selective for cis-9,trans-11-18:2. A commercial CLA methyl ester preparation, containing at least 12 species representing four positional CLA isomers, was incubated in aqueous solution with either a commercial G. candidum lipase preparation (Amano GC-4) or lipase produced from a cloned high-selectivity G. candidum lipase B gene. In both instances selective hydrolysis of the cis-9,trans-11-18:2 methyl ester occurred, with negligible hydrolysis of other CLA isomers. The content of cis-9, trans-11-18:2 in the resulting free fatty acid fraction was between 94 (lipase B reaction) and 77% (GC-4 reaction). The commercial CLA mixture contained only trace amounts of trans-9,cis-11-18:2, and there was no evidence that this isomer was hydrolyzed by the enzyme. Analogous results were obtained with these enzymes in the esterification in organic solvent of a commercial preparation of CLA free fatty acids containing at least 12 CLA isomers. In this case, G. candidum lipase B generated a methyl ester fraction that contained >98% cis-9,trans-11-18:2. Geotrichum candidum lipases B and GC-4 also demonstrated high selectivity in the esterification of CLA with ethanol, generating ethyl ester fractions containing 96 and 80%, respectively, of the cis-9,trans-11 isomer. In a second set of experiments, CLA synthesized from pure linoleic acid, composed essentially of two isomers, cis-9,trans-11 and trans-10,cis-12, was utilized. This was subjected to esterification with octanol in an aqueous reaction system using Amano GC-4 lipase as catalyst. The resulting ester fraction contained up to 97% of the cis-9,trans-11 isomer. After adjustment of the reaction conditions, a concentration of 85% trans-10,cis-12-18:2 could be obtained in the unreacted free fatty acid fraction. These lipase-catalyzed reactions provide a means for the preparative-scale production of high-purity cis-9,trans-11-18:2, and a corresponding CLA fraction depleted of this isomer.

Chemical Fractionation↗

Effect of material deprivation on Epstein-Barr virus infection in Hodgkin's disease in the West Midlands.

We have used Townsend scores from postcode data to compare levels of material deprivation and Epstein-Barr virus (EBV)-positivity for 223 patients diagnosed with Hodgkin's disease (HD) in the period 1981-1997. The presence of EBV in HD tumours was determined using in situ hybridization to target the abundantly expressed EBV early RNAs. EBV was detected in the malignant Hodgkin and Reed-Sternberg cells in 47/223 HD cases (21%). There was found to be a tendency for higher Townsend scores (indicative of higher levels of material deprivation) in EBV-positive HD patients, but this association was not statistically significant. When various subgroups of patients from the study were examined separately the indication of higher Townsend scores in EBV-positive patients was found to be more marked for patients with mixed cellularity disease (P = 0.09) and for females (P = 0.03). The results of this study suggest that differences in the level of material deprivation are important in determining the likelihood of EBV-positive HD in the UK, particularly for certain subgroups of patients. It is not known what specific socioeconomic factors are responsible for these differences, although alterations in the timing or rate of primary EBV infection, or decline in the level of EBV-specific immunity, may be important.

Adolescent↗

Cross-education of muscle strength is greater with stimulated than voluntary contractions.

Cross-education enhances the performance of muscles not directly involved in the chronic conditioning of the muscles in a remote limb. Substantial cross-education occurs after training with eccentric contractions or with contractions evoked by electromyostimulation (EMS). Since during EMS and eccentric contractions, skin and muscle afferents are activated that have excitatory effects on contralateral homologous muscles, it was hypothesized that exercise training with stimulated vs. voluntary eccentric contractions would lead to greater cross-education. Thirty-two women were randomly assigned to a voluntary (Vol), an EMS, or remote EMS (rEMS) exercise group and performed 840 voluntary or stimulated eccentric contractions over 6 weeks. All subjects, including nonexercising controls (Con), were tested pre- and posttraining for maximal voluntary and stimulated isometric and eccentric quadriceps strength. Ipsilateral voluntary and stimulated forces increased in all groups. Changes in EMG activity paralleled those in voluntary force in each limb. No changes occurred in grip strength. The great contra- and ipsilateral strength gains after EMS training were most likely related to an additive effect of EMS and muscle lengthening.

Adult↗