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H Smith

Publications and source records attributed to H Smith.

At least 37 records · Page 2Linked to original sources
PubMed2002

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗
PubMed2002

Approximate solutions of two-way diffusion equations.

In this paper, a general and systematic scheme is formulated for finding approximate solutions of two-way diffusion equations. This expansion scheme is valid for arbitrary mean-free path and can be carried out to any desired accuracy. Its potential is demonstrated by constructing approximate solutions for two problems concerning the kinetics of an electron beam, and the accuracy is found to be very good even when only a few terms are included in the expansion. The approximate solutions found are compared with numerical calculations and previous analytical work in the literature.

Journal Article↗
PubMed2002

Exploitation of the Herpes simplex virus translocating protein VP22 to carry influenza virus proteins into cells for studies of apoptosis: direct confirmation that neuraminidase induces apoptosis and indications that other proteins may have a role.

Previously, we have shown that apoptosis induced by influenza virus was inhibited by an anti-neuraminidase compound [4-guanidino-2, 3-dehydro-N-acetylneuraminic acid (GG167; Relenza; Zanamivir)], which does not enter cells, and acts at the attachment/entry phase of virus replication. Furthermore, a virulent virus, clone 7a, induced greater levels of apoptosis than the attenuated A/Fiji and had greater neuraminidase (NA) activity. To confirm more directly that NA induces apoptosis, the NA of clone 7a and A/Fiji was expressed fused to the Herpes simplex virus tegument coat protein VP22, transfected into HeLa cells and the level of apoptosis determined. VP22 translocates between cells via the medium thus allowing expressed proteins to transfer to a larger number of cells than those originally transfected. Clone 7a NA fused to VP22 induced a significant level of apoptosis whereas A/Fiji NA/VP22 did not, confirming that NA activity is an important determinant of apoptosis acting during fusion protein translocation between cells. Furthermore, the induction of apoptosis was abrogated by antibody to transforming growth factor-beta, which is activated by NA. This approach also showed that VP22/NS1 proteins of both clone 7a and A/Fiji induced apoptosis when expressed alone but inhibited double stranded RNA-induced apoptosis suggesting that this protein may have a dual mode of action. Also, the M1 and M2 proteins of both viruses induced apoptosis but their NP proteins did not.

Apoptosis↗
PubMed2002

A fourth case of 8p11 myeloproliferative disorder transforming to B-lineage acute lymphoblastic leukaemia. A case report.

A 56-year-old male presented with inguinal lymphadenopathy and leucocytosis (WBC 98 x 10(9)/l). Bone marrow morphology showed myeloid hyperplasia, with eosinophilia. Cytogenetic analysis showed no evidence of the Philadelphia chromosome, and fluorescence in situ hybridisation studies for the BCR/ABL fusion were negative. All cells examined showed the t(8;13)(p11;q12) translocation. Six weeks after presentation, the disease progressed to an acute lymphoblastic leukaemia (ALL). The lymphoblasts were CD19/CD10 dual positive. Cytogenetic analysis again showed the t(8;13) translocation, with no additional abnormalities. There have been at least 14 reported cases of the t(8;13) myeloproliferative disorder to date, of which only 3 transformed to B-lineage ALL: our case is the 4th.

Bone Marrow Cells↗
PubMed2001

Activity of human Delta5 and Delta6 desaturases on multiple n-3 and n-6 polyunsaturated fatty acids.

Yeast co-expressing human elongase and desaturase genes were used to investigate whether the same desaturase gene encodes an enzyme able to desaturate n-3 and n-6 fatty acids with the same or different carbon chain length. The results clearly demonstrated that a single human Delta5 desaturase is active on 20:3n-6 and 20:4n-3. Endogenous Delta6 desaturase substrates were generated by providing to the yeast radiolabelled 20:4n-6 or 20:5n-3 which, through two sequential elongations, produced 24:4n-6 and 24:5n-3, respectively. Overall, our data suggest that a single human Delta6 desaturase is active on 18:2n-6, 18:3n-3, 24:4n-6 and 24:5n-3.

Chromatography, High Pressure Liquid↗
PubMed2001

Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis.

High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalenesulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC(50) values in the region of 1-20 nM.

Animals↗
PubMed2001

Motor cortex stimulation for neuropathic pain.

Motor cortex stimulation is increasingly reported in the literature as a surgical option for the alleviation of neuropathic pain. The authors review the published literature and present their results including those demonstrated in a randomized controlled trial that confirmed the efficacy of the procedure. Patient selection and prediction of outcomes, however, remain difficult issues.

Adult↗
PubMed2001

Proximity signal and shade avoidance differences between early and late successional trees.

Competitive interactions between plants determine the success of individuals and species. In developing forests, competition for light is the predominant factor. Shade tolerators acclimate photosynthetically to low light and are capable of long-term survival under the shade cast by others, whereas shade avoiders rapidly dominate gaps but are overtaken in due course by shade-tolerant, later successional species. Shade avoidance results from the phytochrome-mediated perception of far-red radiation (700-800 nm) scattered from the leaves of neighbours, provides early warning of shading, and induces developmental responses that, when successful, result in the overgrowth of those neighbours. Shade tolerators cast a deep shade, whereas less-tolerant species cast light shade, and saplings tend to have high survivorship in shade cast by conspecific adults, but high rates of mortality when shaded by more-tolerant species. Here we report a parallel relationship in which the shade-avoidance responses of three tree species are inversely proportional to proximity signals generated by those species. On this basis, early successional species generate small proximity signals but react strongly to them, whereas late successional species react weakly but generate strong signals.

Ecosystem↗
PubMed2001

Letrozole as primary medical therapy for locally advanced and large operable breast cancer.

AIMS: To investigate the efficacy of letrozole 2.5 mg and 10 mg used as primary neoadjuvant therapy for patients with locally advanced and large operable breast cancer. PATIENTS AND METHODS: Twenty-four postmenopausal patients with locally advanced or large operable breast cancer were treated in two consecutive series with letrozole 2.5 mg (n = 12) or letrozole 10 mg (n = 12). Response at three months was measured by change in tumor volume according to WHO criteria (partial response was defined as a reduction in tumor volume > or = 65%). Tumor volumes were assessed clinically, by ultrasound and mammography, and pathologically. RESULTS: All 24 patients were estrogen receptor-positive, were considered 'receptor-rich', and mean age was 77.6 years and 71.6 years in the letrozole 2.5 mg and 10 mg treatment groups, respectively. There were five complete clinical responses and seven partial clinical responses in the patients treated with 2.5 mg letrozole, and nine partial responses and three patients with stable disease in patients treated with 10 mg letrozole. Assessed by ultrasound and mammography, the 12 patients treated with 2.5 mg had one complete response, nine partial responses and two with no change. In the 12 patients treated with 10 mg letrozole, imaging gave eight partial responses and four with no change. One patient treated with the 2.5 mg dose had a complete clinical and pathological response. There was no significant difference between the two doses in effect on tumor volume, and no recordable side effects associated with either dose. CONCLUSION: Letrozole used in a neoadjuvant setting is highly effective, producing clinically beneficial reductions in tumor volume allowing all patients to have breast conserving surgery, and has an acceptable safety profile.

Aged↗
PubMed2001

A retrospective analysis of contact allergy to lanolin.

BACKGROUND: Lanolin is often stated to be an important sensitizer but some of the available literature is based on the analysis of high-risk patients. OBJECTIVES: To analyse the frequency of contact allergy to lanolin (wool alcohols) in a central London teaching hospital patch-test population. METHODS: Review of 24,449 patients recorded on our database during 1982--96 who were tested with a standard series containing 30% wool alcohols. RESULTS: The mean annual rate of sensitivity to this allergen was 1.7%. The wool alcohols-allergic group contained a higher proportion of females (P < 0.05), and the mean age of both males and females (48.4 and 49.2 years) was higher than that of non-wool alcohols-allergic patients (41.4 and 35.9 years; P < 0.0005). There was no difference in atopic eczema status between these groups. The highest prevalence of allergy to wool alcohols was among patients with lower leg dermatitis (6.0%; 95% confidence interval, CI 4.46--7.54), followed by those with anogenital dermatitis (3.23%; 95% CI 1.81--4.65). There was an unexplained decline in the rate of positive patch tests to Amerchol L-101. However, some patients who reacted to this were negative with wool alcohols, so it may be a useful additional test reagent. The mean rates of allergy to Eucerin (0.65% per annum) and 50% hydrogenated lanolin in petrolatum (1% per annum) were low, and we no longer use these as test reagents. CONCLUSIONS: This study illustrates that lanolin sensitization has remained at a relatively low and constant rate even in a high-risk population (i.e. patients with recent or active eczema).

Adolescent↗
PubMed2001

Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999.

A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by standard methods for susceptibility to antibiotics used for treatment and prophylaxis. The proportion of isolates fully susceptible to penicillin decreased from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less sensitive to penicillin except for two meningococci with a penicillin MIC of 1 mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from 1994 to 1999. There was no significant difference in the geometric mean penicillin MICs of serogroup B and serogroup C meningococci. Penicillin susceptibility was significantly associated with a poorer outcome. Isolates from survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other than the decrease in susceptibility to penicillin observed were more relevant to outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin resistance was infrequent (eight isolates in 6 years) and sporadic. A single isolate had decreased quinolone susceptibility. Despite the significant shift in susceptibility to penicillin recorded, this group of antibiotics remains a suitable treatment for IMD in Australia.

4-Quinolones↗
PubMed2001

Alpha(2) receptors and agonists in pain management.

Alpha(2) agonists have been in clinical use for decades, primarily in the treatment of hypertension. In recent years, alpha(2) agonists have found wider application, particularly in the fields of anesthesia and pain management. It has been noted that these agents can enhance analgesia provided by traditional analgesics, such as opiates, and may result in opiate-sparing effects. This has important implications for the management of acute postoperative pain and chronic pain states, including disorders involving spasticity or myofascial pain, neuropathic pain, and chronic daily headaches. The clinical utility of these agents is ever expanding, as they are gaining broader use in neuraxial analgesia, and new applications are continuously under investigation. The alpha(2) agonists that are currently employed in anesthesia and pain management include clonidine, tizanidine, and dexmedetomidine. Moxonidine and radolmidine, which are not currently in clinical use in humans, may offer favorable side-effect profiles when compared with traditional alpha(2) agonists, and may thereby allow for more widespread pain management applications.

Journal Article↗
PubMed2001

Psychosis and aggression in Alzheimer's disease: the effect of dopamine receptor gene variation.

This study investigated possible associations between selected polymorphisms in the dopamine receptor genes DRD1 and DRD3 with the presence of psychotic phenomena or aggressive behaviour in a community based cohort of 134 patients with late onset Alzheimer's disease. An association was found between the presence of psychotic symptoms and aggressive behaviour and the DRD1 polymorphism and between the presence of psychosis, but not aggression, and the DRD3 polymorphism. Specifically, carriers of the DRD1 B2 allele were more likely to be aggressive or experience hallucinations whereas homozygous carriers of the DRD3 1 allele were more likely to experience delusions.

Age of Onset↗
PubMed2001

Audit of HIV testing: who, why and when?

The risk factors, referral pattern and presence/absence of genital tract symptoms and/or sexually transmitted infections (STIs) in 189 patients having HIV counselling and/or testing at genitourinary medicine (GUM) clinics are reviewed. Eighty per cent were concerned about heterosexual transmission, 9.5% men who have sex with men (MSM) and 4.8% intravenous drug users (IDUs). Heterosexuals and first-time GUM attenders were more likely to have sought prior advice from their general practitioner (GP). The majority were asymptomatic for genital tract infections, but 83% accepted an STI screen, with 44 STIs being diagnosed. Only one individual who had attended primarily for HIV screening was found to have an STI. About half of individuals presented within the window period, and of those stating that they wished to proceed with deferred testing, half subsequently failed to return, resulting in wasted health adviser appointments.

AIDS Serodiagnosis↗