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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 325 records · Page 18Linked to original sources
PubMed1997

Repeat HIV testers at a London same-day testing clinic.

OBJECTIVE: To compare the characteristics of repeat HIV testers with first-time testers in a National Health Service HIV testing clinic in London. SUBJECTS AND METHODS: A self-administered questionnaire was distributed to clinic attenders between September 1995 and January 1996. The sample was stratified by gender and sexual orientation. Repeat and first-time testers were compared with respect to recent sexual risk behaviour, reasons for taking the HIV test, condom use, knowledge of sex partner's HIV status, and sociodemographic and psychosocial variables. RESULTS: Of 965 clinic attenders surveyed, 404 (41.9%) reported at least one previous HIV test outside the window period and were classified as repeat testers: homosexual men, 62.5% (178 out of 285); heterosexual men, 35.1% (126 out of 359); heterosexual women, 31.2% (100 out of 321). Among homosexual men, repeat testers were more likely to report the following: two or more partners in the previous 6 months for both unprotected anal sex (25.8 versus 9.3%; P < 0.01) and unprotected oral sex (53.9 versus 37.4%; P < 0.01); ever having had a sexually transmitted disease (STD) other than HIV (49.4 versus 29.0%; P < 0.01); taking the present test "as part of a regular health check' (48.9 versus 28.0%; P < 0.01); and knowing others who had tested for or been infected with HIV. Repeat testing heterosexual men were more likely to report the following: two or more partners in the previous 6 months for unprotected vaginal sex (42.9 versus 30.9%; P < 0.05) and unprotected oral sex (41.3 versus 25.3%; P < 0.01); ever having had an STD other than HIV (31.7 versus 20.6%; P < 0.05); taking the present test "as part of a regular health check' (36.5 versus 26.2%; P < 0.05); and knowing others who had tested for or been infected with HIV. For heterosexual women, repeat testers were more likely to report ever having had an STD other than HIV (25.0 versus 14.5%; P < 0.05), and knowing others who had tested for or been infected with HIV. CONCLUSIONS: Repeat testing was associated with high-risk sexual behaviour, a previous STD, knowledge of others who have tested for or been infected with HIV, and seeking the test as part of a regular health check. Factors contributing to repeat testing are multi-faceted and vary between groups of different sexual orientation. Use of the impact of knowledge of others infected by HIV and the experience of contracting an STD other than HIV may guide the development of HIV counselling interventions aimed at reducing sexual risk behaviour.

Adult↗
PubMed1997

X-ray crystal structure of cytotoxic oxidized cholesterols: 7-ketocholesterol and 25-hydroxycholesterol.

The cytotoxic cholesterol derivative, 7-ketocholesterol, crystallizes in a monoclinic unit cell, space group P2(1) with a = 11.405 A, b = 6.288 A, c = 35.393 A and beta = 92.75 degrees (Z = 4). Its room temperature crystal structure was solved by direct methods, i.e., the minimal principle via the Shake-and-Bake (SnB) algorithm. In contrast to the continuous chain pattern found for the cholesterol monohydrate structure, hydrogen bonding in the 7-ketocholesterol structure is localized to specific sites via one water molecule that forms linkages between two O3 hydroxyl groups and one keto oxygen. The final weighted R factor for 4562 reflections was 0.144. The 25-hydroxycholesterol also crystallizes in a monoclinic unit cell (P2(1)), with a = 10.840 A, b = 14.533 A, c = 16.093 A and beta = 95.91 degrees (Z = 4). The low temperature structure was solved by DIRDIF. In this instance, molecular packing is anti-parallel in layers stabilized by hydrogen bonding networks via both hydroxyl functions, differing both from cholesterol monohydrate and the 7-ketocholesterol. The final weighted R-factor for 6566 reflections was 0.034. Functional differences of the oxysterols therefore, may be expressed by observed variations in the molecular packing and geometry.

Crystallization↗
PubMed1997

The Virtual Microscope.

We present the design of the Virtual Microscope, a software system employing a client/server architecture to provide a realistic emulation of a high power light microscope. We discuss several technical challenges related to providing the performance necessary to achieve rapid response time, mainly in dealing with the enormous amounts of data (tens to hundreds of gigabytes per slide) that must be retrieved from secondary storage and processed. To effectively implement the data server, the system design relies on the computational power and high I/O throughput available from an appropriately configured parallel computer.

Computers↗
PubMed1996

Results of a survey of equine practitioners on the use and perceived efficacy of polysulfated glycosaminoglycan.

OBJECTIVE: To determine the patterns of use and perceived efficacy of polysulfated glycosaminoglycan (PSGAG) for the treatment of degenerative joint disease in horses. DESIGN: Cross-sectional mail survey. SAMPLE POPULATION: 1,522 equine practitioners. PROCEDURE: Information was obtained on frequency and route of administration of PSGAG for the treatment of each of 4 forms of degenerative joint disease, the efficacy of PSGAG, and its efficacy compared with that of sodium hyaluronate. Data were analyzed by nonparametric and multivariate regression methods. RESULTS: Response rate was 40.5%. Of practitioners responding, 26% were classified as having a special interest in lameness and 74% as general practitioners. Use of PSGAG was reported by 90.5% of all practitioners, but lameness practitioners used PSGAG more frequently than general practitioners. Use of PSGAG also was significantly more common among practitioners involved predominately with racing. Thoroughbreds, Standardbreds, or show horses. Use of PSGAG was reported to be moderately effective in the treatment of the 4 joint disease conditions. Practitioners treating Thoroughbred racehorses gave highest efficacy scores, and pleasure horse practitioners gave lowest efficacy scores. Use of PSGAG was considered more effective than sodium hyaluronate for the treatment of subacute degenerative joint disease and less effective for idiopathic joint effusion and acute synovitis. CLINICAL IMPLICATIONS: Use of PSGAG is regarded as moderately effective overall and is considered most useful in the treatment of subacute degenerative joint disease. The efficacy of PSGAG for incipient and chronic forms of degenerative disease is considered comparable to that of sodium hyaluronate.

Animals↗
PubMed1996

Structure-activity relationships of the antimalarial agent artemisinin. 5. Analogs of 10-deoxoartemisinin substituted at C-3 and C-9.

Novel 3- and 9-substituted analogs (4-19) of 10-deoxoartemisinin, 3, were prepared from the corresponding known lactones by one-pot reduction with sodium borohydride and boron trifluoride etherate. Reproducibility problems associated with this heterogeneous reaction were encountered on small reaction scales, and thus alternative methodology was sought for this reduction. Conversion of the lactones to tetrahydropyrans via the corresponding intermediate lactols was made more reproducible using a two-step sequence involving low-temperature reduction with diisobutylaluminum hydride followed by deoxygenation with boron trifluoride etherate in the presence of triethylsilane. In this manner, 10-deoxoartemisinin (3) could be obtained from artemisinin (1) in greater than 95% overall yield. All analogs were tested in vitro against W-2 and D-6 strains of Plasmodium falciparum. Several of the analogs were much more active than the natural product (+)-artemisinin (1) or 10-deoxoartemisinin (3). Conventional structure-activity relationships are discussed in relation to the bioassay data.

Animals↗
PubMed1996

Relaxed specificity of matrix metalloproteinases (MMPS) and TIMP insensitivity of tumor necrosis factor-alpha (TNF-alpha) production suggest the major TNF-alpha converting enzyme is not an MMP.

Tumor necrosis factor-alpha is released from cells by a proteolytic cleavage. Previous work suggested that a specific, non-matrix metalloproteinase carries out this cleavage, but matrix metalloproteinases have also been implicated. In this paper, we report that none of the matrix metalloproteinases tested cleaved peptide substrates as specifically as the non-matrix metalloproteinase. A matrix metalloproteinase did process tumor necrosis factor-alpha extracted from COS cells, but neither tissue inhibitor of metalloproteinases-1 nor -2 blocked tumor necrosis factor-alpha processing by human monocytes. Moreover, tissue inhibitor of metalloproteinases-1 had at most a partial effect on the in vivo release of the cytokine in mice. We conclude that a non-matrix metalloproteinase is the major physiological tumor necrosis factor-alpha convertase.

ADAM Proteins↗
PubMed1996

The pleckstrin homology domain of human beta I sigma II spectrin is targeted to the plasma membrane in vivo.

We have examined the in vivo targeting potential of the Pleckstrin Homology (PH) domain from human beta I sigma II spectrin using a novel Aequoria victoria green fluorescent protein (GFP) fusion vector constructed from a human codon optimized cDNA. This vector efficiently expresses both GFP and the GFP spectrin fusion protein in COS7 and other cell lines. GFP expressed alone shows only diffuse cytoplasmic staining which is not associated with the plasma membrane. In contrast the GFP-beta I sigma II spectrin PH domain fusion protein localizes under the plasma membrane of transfected COS7 cells in vivo. Fixation of cells transfected with GFP alone in -20 degrees C methanol results in the removal of all specific fluorescence. In contrast cells transfected with the GFP-beta I sigma II spectrin construct and fixed -20 degrees C methanol continue to show strong membrane fluorescence, consistent with a role for the spectrin PH domain in membrane localization in vivo.

Amino Acid Sequence↗
PubMed1996

HIV-associated respiratory diseases.

The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours; over two-thirds of patients have at least one respiratory episode during the course of their disease. Despite the availability of effective prophylaxis, infection with the fungus Pneumocystis carinii remains a common cause of respiratory disease. Bacterial infections, which occur more frequently in HIV-infected persons than in the general population, and tuberculosis are increasing causes of morbidity and mortality. Kaposi's sarcoma, the commonest HIV-associated malignancy, may affect the lungs in addition to the skin. Pulmonary involvement by non-Hodgkin lymphoma is common in those with disseminated disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

Management of thyroid carcinoma with radioactive 131I.

PURPOSE: To evaluate the role of radioactive 131I in the management of patients with well differentiated carcinoma of the thyroid. METHODS AND MATERIALS: Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131I. RESULTS: With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131I therapy. CONCLUSIONS: Radioactive 131I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131I.

Adolescent↗
PubMed1996

Structure-activity relationships of the antimalarial agent artemisinin. 4. Effect of substitution at C-3.

Novel antimalarial artemisinin analogs, 3-alkylartemisinins as well as 3-(arylalkyl)- and 3-(carboxyalkyl)artemisinins, were prepared via the synthetic intermediate 2. Formation of the N,N-dimethylhydrazones 5 and 24 and then regio- and chemoselective deprotonation followed by alkylation provided initially alkylated hydrazones that upon chromatography gave ketones 6-13 and 25-30. Direct ozonolysis of the ketones followed by in situ acidification lead directly to the formation of title compounds 14-21 and 31-36. The analogs were tested in vitro against W-2 and D-6 strains of Plasmodium falciparum and found to be in some cases much more active than the natural product (+)-artemisinin. The results were included in structure-activity relationship (CoMFA) studies for further analog design.

Animals↗
PubMed1996

Structure-activity relationships of the antimalarial agent artemisinin. 3. Total synthesis of (+)-13-carbaartemisinin and related tetra- and tricyclic structures.

Provided by total synthesis, endoperoxides 18, 20, and 22 underwent intramolecular oxymercuration-demercuration leading respectively to formation of an isomeric tetracycle, (1aS, 3S, 5aS, 6R, 8aS, 9R, 12S)-10-deoxo-13-carbaartemisinin (19), (+)-10-deoxo-13-carbaartemisinin (21), and (+)-13-carbaartemisinin (4). Structure assignment to 19 and 21 was based on single-crystal X-ray crystallographic analysis. Tricyclic endoperoxide 20 was converted to methyl and benzyl ethers 23 and 24 and reduced to saturated analog 25 which was also converted to ethers 26 and 27. In vitro antimalarial screening of both tri- and tetracyclic analogs was conducted using the W-2 and D-6 clones of Plasmodium falciparum. Neither target 4 nor 21 displayed substantial antimalarial potency in vitro against P. falciparum, but the diastereomeric peroxide 19 possessed good antimalarial potency in vitro. Tricyclic analogs were uniformly impotent. Iron(II) bromide-promoted rearrangement of 21 gave, in 79% yield, the unique tetracyclic alcohol 35, while 19 provided ring-opened cyclohexanone 41 (39%) along with the tricyclic epoxide 42 (20%). Neither 41 nor 42 possessed in vitro antimalarial activity, suggesting that epoxide-like intermediates are not responsible for the mode of action of this subclass of antimalarials. Rearrangement of 10-deoxoartemisinin (43) with FeBr2 gave a major product (79%) not encountered in the rearrangement of artemisinin that resulted from unraveling of the tetracyclic system cyclohexanone 46. Minor amounts of 1,10-dideoxoartemisinin (49) (8%) were also produced in this reaction.

Animals↗
PubMed1996

Environmental enhancement of growth factor-mediated oligodendrocyte precursor proliferation.

The timing of oligodendrogenesis depends on the specific location within the central nervous system, suggesting the local environment influences oligodendrocyte precursor proliferation. Spinal cord and optic nerve oligodendrocyte precursors both proliferate in response to platelet-derived growth factor (PDGF). Here we show that neurotrophin-3 (NT-3) enhanced PDGF-induced proliferation of optic nerve oligodendrocyte precursors, and these cells were labeled by an anti-trkC antibody. By contrast, NT-3 did not enhance PDGF-induced proliferation of spinal cord oligodendrocyte precursors, and these cells were not labeled by an anti-trkC antibody. Furthermore, PDGF-induced oligodendrocyte precursor proliferation was greater in spinal cord than in optic nerve cultures. The difference in NT-3 response between spinal cord and optic nerve oligodendrocyte precursors appears cell intrinsic, while the enhanced PDGF-induced proliferation of spinal cord oligodendrocyte precursors appears environmentally regulated. The spinal cord PDGF proliferation-enhancing activity may provide a mechanism to allow temporal and spatial regulation of gliogenesis.

Animals↗
PubMed1996

Neural assemblies and laminar interactions in the cerebral cortex.

Neural assemblies are assumed to become organized and to operate within the cerebral cortex, and so must be constrained by the cytological and physiological properties of this laminated structure. A hypothesis of such assemblies is presented, based on important details of neuronal architecture and physiology in different cortical laminae. Laminae II, III and VI, which are the origin and termination of most cortico-cortical projections, are regarded as the site of storage of most of the information encoded by assemblies - a neuronal 'library'. Laminae II and III are the most sensitive coincidence detectors, and therefore probably initiate the process of assembly formation. However, these three laminae have very low levels of spontaneous activity in the waking state, and so active cell assemblies cannot base their functioning on these laminae alone. Lamina V pyramidal cells have a much higher level of spontaneous activity. Thus, indirect pathways between 'library' cells, via lamina V pyramidal cells, are likely to be more secure than direct ones. It is proposed that direct links between 'library' cells become stabilized by Hebbian strengthening, once the recipient 'library' cell has been 'primed' by neural activity transmitted indirectly via lamina V neurones. Thus lamina V neurones could catalyse the process of assembly formation. Given this proposal, lamina V cells, in their interaction with 'library' cells, would code information in terms of precisely timed individual impulses, but would employ a code based on slower frequency changes in their descending influences upon neural centres in the brainstem and spinal cord. Predictions for single unit and electrographic experiments are discussed.

Afferent Pathways↗