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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 289 records · Page 16Linked to original sources
PubMed1999

Protection of neuronal cells from apoptosis by Hsp27 delivered with a herpes simplex virus-based vector.

Overexpression of the gene encoding the 70-kDa heat shock protein (hsp70) has previously been shown to protect neuronal cells against subsequent thermal or ischemic stress. It has no protective effect, however, against stimuli that induce apoptosis, although a mild heat shock (sufficient to induce hsp synthesis) does have a protective effect against apoptosis. We have prepared disabled herpes simplex virus-based vectors that are able to produce high level expression of individual hsps in infected neuronal cells without damaging effects. We have used these vectors to show that hsp27 and hsp56 (which have never previously been overexpressed in neuronal cells) as well as hsp70 can protect dorsal root ganglion neurons from thermal or ischemic stress. In contrast, only hsp27 can protect dorsal root ganglion neurons from apoptosis induced by nerve growth factor withdrawal, and hsp27 also protects the ND7 neuronal cell line from retinoic acid-induced apoptosis. However, hsp70 showed no protective effect against apoptosis in contrast to its anti-apoptotic effect in non-neuronal cell types. These results thus identify hsp27 as a novel neuroprotective factor and show that it can mediate this effect when delivered via a high efficiency viral vector.

Animals↗
PubMed1999

A detailed study of the substrate specificity of a chimeric restriction enzyme.

Recently, the crystal structure of the designed zinc finger protein, DeltaQNK, bound to a preferred DNA sequence was reported. We have converted DeltaQNK into a novel site-specific endonuclease by linking it to the Fok I cleavage domain (FN). The substrate specificity and DNA cleavage properties of the resulting chimeric restriction enzyme (DeltaQNK-FN) were investigated, and the binding affinities of DeltaQNK and DeltaQNK-FN for various DNA substrates were determined. Substrates that are bound by DeltaQNK with high affinity are the same as those that are cleaved efficiently by DeltaQNK-FN. Substrates bound by DeltaQNK with lower affinity are cleaved with very low efficiency or not at all by DeltaQNK-FN. The binding of DeltaQNK-FN to each substrate was approximately 2-fold weaker than that for DeltaQNK. Thus, the fusion of the Fok I cleavage domain to the zinc finger motif does not change the DNA sequence specificity of the zinc finger protein and does not change its binding affinity significantly.

Amino Acid Sequence↗
PubMed1999

Primary care groups. Supra troupers.

Research in Birmingham involving GPs, the health authority and the local medical committee found support for umbrella arrangements for some primary care group functions. Clinical governance and strategic city-wide planning emerged as particularly suitable for these arrangements. A range of support arrangements are likely to emerge as PCGs develop.

Governing Board↗
PubMed1999

Impact of resident feedback on immunization outcomes.

OBJECTIVE: To investigate the effect on immunization levels of retrospective written feedback to residents regarding missed immunization opportunities. DESIGN: Randomized trial with control group. SETTING: Pediatric resident continuity clinic in an urban hospital-based primary care clinic. PARTICIPANTS: Thirty-two postgraduate level 2 and postgraduate level 3 pediatric residents. INTERVENTION: Monthly retrospective written feedback mailed to residents detailing their missed immunization opportunities and appointment failure rates over a 12-month period beginning in February 1997. MAIN OUTCOME MEASURES: The immunization level of 2-year-old children in the resident clinic was the main outcome of interest. Secondary outcomes included missed immunization opportunity rates and appointment failure rates. RESULTS: Postintervention immunization levels were 71.4% (95% confidence limits [CLs]: 63.2%, 78.7%) for patients from the intervention group and 68.5% (95% CLs: 60.8%, 75.4%) for patients from the control group. The immunization level for patients of both groups who had fewer than 2 visits during the second year of life was 47.2% (95% CLs: 38.2%, 56.3%). This compares with an immunization level of 78.1% (95% CLs: 66.0%, 87.5%) for patients from both groups who had 2 visits during the second year of life, and with an immunization level of 88.2% (95% CLs: 81.0%, 93.4%) for patients of both groups who had more than 2 visits during the second year of life (P<.001). CONCLUSIONS: In this setting, written retrospective feedback to residents was an ineffective strategy for improving immunization levels. Adequate follow-up during the second year of life is critical in achieving high immunization levels.

Adult↗
PubMed1999

The effects of knee extensor and flexor muscle training on the timed-up-and-go test in individuals with rheumatoid arthritis.

BACKGROUND AND PURPOSE: Rheumatoid arthritis frequently results in functional impairment. This study investigated the effect of a specific exercise regimen on function. METHOD: A randomized controlled assessor-blinded (N = 36) compared the effect of knee extensor and flexor muscle training on pain, the timed up and go (TUG) test and the Health Assessment Questionnaire in subjects with non-acute rheumatoid arthritis. RESULTS: Knee extensor and flexor muscle training increased isokinetic torques at speeds of 60 degrees/sec-1 and 120 degrees/sec-1 as measured by an isokinetic dynamometer (p = 0.02-0.003). The experimental group experienced a reduction in pain (p = 0.03), an improvement in TUG time (p = 0.01) and in function as measured by the Health Assessment Questionnaire (p = 0.04). CONCLUSIONS: Specific knee muscle training can be administered safely in people with non-acute rheumatoid arthritis, and may produce functional benefits.

Activities of Daily Living↗
PubMed1999

Effects of the aromatase inhibitor Fadrozole on plasma sex steroid secretion and ovulation rate in female coho salmon, Oncorhynchus kisutch, close to final maturation.

Plasma levels of 17beta-estradiol, 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-P), and testosterone were measured in adult female coho salmon in late vitellogenesis, approximately 1.5 months before spawning and just before and following intraperitoneal injection with the aromatase inhibitor (AI) Fadrozole. Injection at dosages of 0.1, 1.0, and 10.0 mg AI/kg body wt caused a significant drop in plasma 17beta-estradiol levels relative to preinjection values within 3 or 6 h. Injection of 10 mg AI/kg body wt caused a significant increase in plasma 17alpha-20beta-P levels within 3 h. Ten days after injection 67% of the fish treated with 10 mg AI/kg body wt had ovulated in contrast with 0% in the group injected with 0.1 mg AI/kg body wt. The fertilization rate of the eggs varied between 96% in the control group and 85% in the groups injected with AI. We conclude that the shift from 17beta-estradiol to 17alpha,20beta-P biosynthesis, which is characteristic of maturing Oncorhynchus sp., was advanced significantly by treatment with AI and that Fadrozole can be used as a tool to investigate periovulatory endocrine changes in salmon.

Animals↗
PubMed1999

Synchronous Paget's sarcoma of tibiae in which Paget's disease was limited to these bones.

A 51-year-old native of Rio de Janeiro presented with bilateral synchronous Paget's sarcomas in the tibiae, which developed in the upper right tibia and in the distal third of the left tibia. There were no other areas of Paget's disease. The largest tumor spread to the right inguinal nodes and also soft tissue. The tumor in the left tibia spread dramatically in the soft tissues up the leg and only involved the medullary cavity in its inferior portion. The patient died, but there was no autopsy. Comments are made about the prevalence of Paget's disease in Rio de Janeiro.

Bone Neoplasms↗
PubMed1999

Musculoskeletal rehabilitation and sports medicine. 2. Shoulder and upper extremity injuries.

This self-directed learning module discusses classic concepts and highlights new advances in the diagnosis and management of shoulder and upper extremity injuries commonly occurring from athletic competition. It is part of the chapter on musculoskeletal rehabilitation and sports medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation.

Adult↗
PubMed1999

Musculoskeletal rehabilitation and sports medicine. 4. Miscellaneous sports medicine topics.

This self-directed learning module highlights new advances in this topic area. It is part of the chapter on musculoskeletal rehabilitation and sports medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article discusses physiatric duties as a team physician, preparticipation physical examinations, ergogenic aids, heat-related illness, pediatric sports injuries, female sports injuries, and sports medicine topics pertinent to geriatric and physically or mentally challenged athletes. New advances covered in this section include use of creatine, guidelines for the preparticipation examination, sudden cardiac athletic death, pediatric and female anterior cruciate ligament injuries, the female athlete triad, spine screening in Down syndrome athletes, and "boosting" in athletes with spinal cord injury.

Adult↗
PubMed1999

The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice.

OBJECTIVE: To investigate the possible mechanisms of the antiatherosclerotic effects of the angiotensin-converting enzyme (ACE) inhibitor, fosinopril, in apolipoprotein (apo) E deficient mice. METHODS: Apo E deficient (E0) mice at the age of 8 weeks received either placebo or a high dose (25 mg/kg/d) of fosinopril supplemented in their drinking water. RESULTS: After 12 weeks of treatment, fosinopril reduced the aortic lesion size by 70%, compared with the placebo group. At this dosage, fosinopril significantly reduced blood pressure from 93 +/- 2 mmHg before treatment to 70 +/- 2 mmHg at the end of the treatment period (P < 0.005). Fosinopril also increased the resistance of the mice plasma low density lipoprotein (LDL) to CuSO4-induced oxidation, as shown by a 90% reduction in the LDL content of malondialdehyde (MDA) and also by a prolongation of the lag time required for the initiation of LDL oxidation (from 100 min in the placebo-treated mice to more than 240 min in the fosinopril-treated mice; P < 0.001). In addition, fosinopril inhibited CuSO4-induced oxidation of LDL that was obtained from the aortas of the treated mice, as shown by an 18% and 37% reduction in the LDL content of lipid peroxides and hydroperoxy-cholesterol linoleate, respectively, compared with the placebo-treated mice (P < 0.01). A low dosage of fosinopril (5 mg/kg/d) that was still adequate to reduce their plasma ACE activity and LDL propensity to lipid peroxidation was insufficient to lower their blood pressure. This dosage also reduced the aortic lesion size in the apo E deficient mice by 40% (P < 0.01). CONCLUSIONS: The antiatherogenic effects of fosinopril in apo E deficient mice are due not only to blood pressure reduction but also to the direct inhibition of angiotensin II-dependent effects, which are probably also associated with the inhibition of LDL oxidation.

Angiotensin Receptor Antagonists↗
PubMed1999

A randomised phase III study of accelerated or standard fraction radiotherapy with or without concurrent carboplatin in inoperable non-small cell lung cancer: final report of an Australian multi-centre trial.

PURPOSE: To investigate the effects separately and together of (a) shortening overall treatment time and (b) giving concurrent carboplatin in patients having radical radiotherapy for inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between April 1989 and May 1995, 204 patients with medically inoperable or technically unresectable NSCLC localised to the primary site and regional lymph nodes were randomised to receive one of four treatments using a 2 x 2 factorial design: standard radiotherapy, 60 Gy in 30 fractions in 6 weeks (R6); accelerated radiotherapy, 60 Gy in 30 fractions in 3 weeks (R3); standard radiotherapy as in R6 with carboplatin 70 mg/m2/day for 5 days during weeks 1 and 5 of radiotherapy (R6C); accelerated radiotherapy as in R3 with carboplatin 70 mg/m2/day for 5 days during week 1 of radiotherapy (R3C). RESULTS: The estimated median survival of all randomised patients was 15.7 months and estimated 2-year survival was 31%. The longest survival was seen in patients randomised to R6C (median 20.3 months, 41% surviving at 2 years) but there were no statistically significant differences between treatment arms or treatment factors (carboplatin versus no carboplatin, accelerated versus conventional radiotherapy). Haematological toxicity was significantly greater in patients treated with carboplatin and oesophageal toxicity was significantly greater and more protracted in patients treated with accelerated radiotherapy. CONCLUSIONS: This study failed to show a significant survival advantage for any of the treatment arms or factors. Halving overall treatment time resulted in significantly greater oesophageal toxicity with no suggestion of a survival advantage.

Adult↗
PubMed1999

T-box genes: what they do and how they do it.

Brachyury is the founder member of the T-box family of transcription factors, which is characterized by a DNA-binding domain of approximately 200 amino acids. Members of the T-box gene family play important roles in the development of both vertebrate and invertebrate embryos, including the control of gastrulation, development of the heart, and perhaps even the decision as to whether to form arm or leg. An understanding of how the T-box genes act requires analysis of how their expression is controlled, identification of their target genes, and an insight into how different family members exert different effects.

Animals↗
PubMed1999

Domestic violence against women in the international community.

The social, economic, legal, and linguistic isolation that women in the international community often endure may make it more difficult for them to seek medical, legal, or social assistance in an effort to free themselves from abusive domestic situations. This article describes and defines potentially dangerous domestic situations and discusses the role of the emergency department in lessening the global health threat of violence among women.

Communication Barriers↗
PubMed1999

Design and synthesis of thrombin receptor-derived nonpeptide mimetics utilizing a piperazine scaffold.

Focal thrombus formation and vasoconstriction serve to defend vessels when vascular damage occurs, but may be detrimental when an atherosclerotic plaque is disrupted. Recently, the identification of the platelet thrombin receptor opened a new area in the development of agents that may selectively inhibit the effects of thrombin on cells, without affecting fibrin formation. In this regard, we have synthesized a number of 1,4-disubstituted piperazines which are designed to be analogues of thrombin receptor activating peptides (TRAP) and carry the pharmacophoric features of Phe and Arg residues present in the active pentapeptide SFLLR. These compounds were tested in the rat aorta relaxation assay and in platelet aggregation studies and their biological activity was consistent with a direct action on thrombin receptor. Furthermore, the structure activity relationships confirmed the importance of Phe and Arg for receptor activation and the molecular modeling revealed an intriguing relationship between their amphipathic similarity with SFLLR and their biological activity.

Animals↗
PubMed1999

The survey form of SCAN: the feasibility of using experienced lay survey interviewers to administer a semi-structured systematic clinical assessment of psychotic and non-psychotic disorders.

BACKGROUND: The success of large scale surveys depends on well designed questionnaires and the skills of lay interviewers. Discrepancies in prevalence rates between epidemiological surveys and poor agreement between survey interviewer and clinician diagnostic interviews are giving rise to increasing concern among researchers, public health planners and policy developers. New approaches to information collection are called for. The feasibility of training experienced survey interviewers in semi-structured, clinical, diagnostic interviewing has never been investigated systematically across the range of neurotic and psychotic disorders. METHODS: Eight experienced survey interviewers from the Office for National Statistics (ONS) were selected and underwent extended training in a Survey Form of SCAN (SCAN-SF). Sixty-four adults, including a majority of psychiatric in-patients were assessed by ONS interviewers and reinterviewed within a week by SCAN-trained clinicians. Feedback was sought from interviewers and trainers. RESULTS: Trainers found lay interviewers coped at least as well with psychotic as with neurotic symptoms. Concordance for any disorder was 0.74 (95% CI: 0.57 to 0.91); for any specific psychotic disorder 0.63 (0.40 to 0.86); for any specific neurotic disorder 0.63 (0.43 to 0.83). Sensitivity ranged from 0.6 to 0.9 and specificity from 0.8 to 0.9. There was no evidence of rater bias. CONCLUSIONS: These preliminary findings are very promising. However, before the SCAN-SF, administered by carefully trained lay interviewers, can be recommended in large scale surveys, further evaluations of its feasibility and reliability in the general population are needed.

Adaptation, Psychological↗
PubMed1999

Early attempts at production of prawn cell lines.

This report describes some unsuccessful attempts to produce continuous cell lines from penaeid prawn tissues in the late 1980s. This information is presented so that others might save time by not repeating the unsuccessful measures that were attempted. The osmolarity of Penaeus monodon haemolymph was measured at 687 mOsmol/kg (N = 10). Of the media tested, the best medium for cell growth and maintenance was shown to be double strength L-15, supplemented with 10% foetal bovine serum, and 10% prawn muscle extract at 28 degrees C ( approximately 675.5 mOsmol/kg). Prawn muscle extract was made by homogenizing 30 g of prawn muscle in 50/50 ratio of distilled water/autoclaved seawater, clarified stepwise by centrifugation at 2k, 14k, 14k xg for 30 minutes each. The resultant supernatant was heat-inactivated on occasions with no improvement in growth. Preconditioned medium, cholesterol, galactose and trehalose supplements and the use of Cell-Tak did not improve growth conditions, and haemolymph extracts were detrimental to the cells. In addition it was shown that Nunc 25 cm(2) plastic culture flasks were better than Linbro and both were better than glass as substrates. The fate of 101 individual primary cell cultures, established from penaeid prawns, was as follows. Fifteen of the cultures succumbed to bacterial contamination, five became contaminated with fungi, four with thauastrochytrids, four succumbed to presumptive viral autocultures and two to ciliate contamination. Cell cultures derived from heart tissue could be maintained for a mean of 12.7 days (sd 9.7d), those derived from the epidermis 15.6 days (sd 9.0d), ovarian tissue 10 days (sd 2d), lymphoid organ 6.8 days (sd 0.4d), nerve cord and hepatopancreas 2 days. The most persistent cell cultures -- those derived from the heart explants -- contained dividing cells at 40 days, and epidermis cells were still dividing at 30 days. The longest lasting, non- proliferating, but viable, cell cultures were those of subcutis/epidermis and heart cells which remained viable for 240 and 307 days respectively. Only cell cultures from multiple prawns achieved 100% confluency in 25 cm(2) plastic culture flasks. No cultures survived attempts at passage by either trypsinisation or mechanical disruption with a rubber policeman. No cell lines were established.

Animals↗