Biomedical subjects

C Alexander

Publications and source records attributed to C Alexander.

At least 19 recordsLinked to original sources

PubMed1992

Sequence of the tufA gene encoding elongation factor EF-Tu from Thermus aquaticus and overproduction of the protein in Escherichia coli.

The sequence of the tufA gene from the extreme thermophilic eubacterium Thermus aquaticus EP 00276 was determined. The GC content in third positions of codons is 89.5%, with an unusual predominance of guanosine (60.7%). The derived protein sequence differs from tufA- and tufB-encoded sequences for elongation factor Tu (EF-Tu) of Thermus thermophilus HB8, another member of the genus Thermus, in 10 of the 405 amino acid residues. Three exchanges are located in the additional loop of ten amino acids (182-191). The loop, probably involved in nucleotide binding, is absent in EF-Tu of the mesophile Escherichia coli. Since EF-Tu from E. coli is quite unstable, the protein is well-suited for analyzing molecular changes that lead to thermostabilization. Comparison of the EF-Tu domain I from E. coli and Thermus strains revealed clustered amino acid exchanges in the C-terminal part of the first helix and in adjacent residues of the second loop inferred to interact with the ribosome. Most other exchanges in the guanine nucleotide binding domain are located in loops or nearest vicinity of loops suggesting their importance for thermostability. The T. aquaticus EF-Tu was overproduced in E. coli using the tac expression system. Identity of the recombinant T. aquaticus EF-Tu was verified by Western blot analysis, N-terminal sequencing and GDP binding assays.

Amino Acid Sequence↗

PubMed1992

Epidermal growth factor (EGF)-stimulated tyrosine phosphorylation and EGF receptor degradation in cells expressing EGF receptors truncated at residue 973.

Epidermal growth factor (EGF)-stimulated tyrosine phosphorylation of proteins was examined in cells expressing wild-type (WT-EGFR) EGF receptors or EGF receptors truncated at residue 973 (973-EGFR). A much broader spectrum of tyrosine phosphorylated proteins was found following EGF treatment of 973-EGFR expressing cells compared with cells expressing wild-type receptors. Several additional ras GTPase activating protein-associated tyrosine phosphorylated proteins were found in EGF-treated 973-EGFR cells relative to WT-EGFR cells. Additional tyrosine-phosphorylated proteins were also found to co-immunoprecipitate with phospholipase C gamma 1 (PLC gamma 1) following EGF treatment of cells expressing 973-EGFR relative to cells expressing WT-EGFR. EGF-stimulated tyrosine phosphorylation of PLC gamma 1 was found in cells expressing WT-EGFR, but not in cells expressing 973-EGFR. WT-EGF receptor from EGF-treated cells bound well to bacterially expressed src homology (SH) regions of PLC gamma 1 and to a lesser extent to bacterially expressed GTPase activating protein SH regions. No binding of 973-EGF receptor to SH regions of either protein could be detected. EGF treatment greatly reduced the half-life of WT-EGFR, but had relatively little effect on the half-life of 973-EGFR. EGF induced internalization of 973-EGFR at a slower rate than WT-EGFR and caused the appearance of discrete receptor degradation products for both cell types. The data indicate that truncation of the EGF receptor at residue 973 alters receptor substrate specificity, decreases the rate of receptor internalization, and has an inhibitory effect on receptor degradation.

3T3 Cells↗

PubMed1992

The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons.

The pattern of retrograde axonal transport of the target-derived neurotrophic molecule, nerve growth factor (NGF), correlates with its trophic actions in adult neurons. We have determined that the NGF-related neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are also retrogradely transported by distinct populations of peripheral and central nervous system neurons in the adult. All three 125I-labeled neurotrophins are retrogradely transported to sites previously shown to contain neurotrophin-responsive neurons as assessed in vitro, such as dorsal root ganglion and basal forebrain neurons. The patterns of transport also indicate the existence of neuronal populations that selectively transport NT-3 and/or BDNF, but not NGF, such as spinal cord motor neurons, neurons in the entorhinal cortex, thalamus, and neurons within the hippocampus itself. Our observations suggest that neurotrophins are transported by overlapping as well as distinct populations of neurons when injected into a given target field. Retrograde transport may thus be predictive of neuronal types selectively responsive to either BDNF or NT-3 in the adult, as first demonstrated for NGF.

Animals↗

PubMed1992

Prediction criteria for successful weaning from respiratory support: statistical and connectionist analyses.

OBJECTIVE: To develop predictive criteria for successful weaning of patients from mechanical assistance to ventilation, based on simple clinical tests using discriminant analyses and neural network systems. DESIGN: Retrospective development of predictive criteria and subsequent prospective testing of the same predictive criteria. SETTING: Medical ICU of a 300-bed teaching Veterans Administration Hospital. PATIENTS: Twenty-five ventilator-dependent elderly patients with acute respiratory failure. INTERVENTIONS: Routine measurements of negative inspiratory force, tidal volume, minute ventilation, respiratory rate, vital capacity, and maximum voluntary ventilation, followed by a weaning trial. Success or failure in 21 efforts was analyzed by a linear and quadratic discriminant model and neural network formulas to develop prediction criteria. The criteria developed were tested for predictive power prospectively in nine trials in six patients. RESULTS: The statistical and neural network analyses predicted the success or failure of weaning within 90% to 100% accuracy. CONCLUSION: Use of quadratic discriminant and neural network analyses could be useful in developing accurate predictive criteria for successful weaning based on simple bedside measurements.

Aged↗

PubMed1992

[A phosphine-substituted diphosphonic acid (HMPD) for improved scintigraphic detection of bone lesions].

Although the radiopharmaceuticals used for bone scintigraphy are of very high quality, the search for an "ideal" agent continues. To optimise the detectability of bone lesions, we analysed 244 different 99mTc-labeled phosphonates in animal experiments. In osteosarcoma-carrying rats 99mTc-labeled 1-Hydroxy-3-methyl-phosphinic-1, 1-propanediphosphonic acid (HMPD) was shown to produce the best lesion/normal bone ratio. 99mTc-MDP was used as reference. The ratio was found to be 1.28 for 99mTc-HMPD. The transferability of our results in animals to the situation in man was studied in 10 patients with bone metastases. There was for 99mTc-HMPD an improvement of the lesion/normal bone ratio by more than 60% but also an additional reduction of the soft tissue contrast by about 40%. 15% of the metastases were detected by scintigraphy using 99mTc-HMPD only and not with 99mTc-MDP. The new agent should make possible a better and earlier discrimination of bone lesions in the scintigram.

Aged↗

PubMed1992

[The detection of inflammation and the formation of HAMA following the administration of monoclonal antibody BW 250/183].

Experiences with the use of the 99mTc-labelled MAb BW 250/183 in the detection of inflammatory lesions are reported. In 160 of 354 investigated patients the results could be confirmed by other methods. The sensitivity (91%) and the specificity (82%) were very high for a diagnostic tool and were comparable with the results of other leukocyte scans as reported in the literature. The positive predictive value of the method was 93%. In 84 patients studied once and in 6 patients studied twice only one case of the latter group showed a positive HAMA response. It may be concluded that the detection of foci of inflammation with the 99mTc-labelled MAb BW 250/183 is of great diagnostic value and that its administration can be repeated without risk.

Adult↗

PubMed1991

[Initial experiences with a new monoclonal antibody in diagnosis of malignant melanomas].

In a study of 17 patients with malignant melanomas in the extremities the sensitivity and specificity of a new monoclonal antibody directed at melanoma cells (BW 575, Behring) were investigated. The specificity was 100%, but the sensitivity 70%. In 3 cases known foci could not be detected. All nodular melanomas and their metastases were detected (9 patients). Repeated examination during the first 24 h after injection of the Tc-99m-marked antibody, and two-plane investigations made it possible to detect even small tumors less than 1 cm in diameter and subcutaneous lesions where the melanomas absorbed the antibodies. Due to its high specificity, the antibody seems to be a promising aid in deciding the operative strategy.

Adult↗

PubMed1991

PTFE or HUV for femoro-popliteal bypass: a multi-centre trial.

Despite wide clinical experience the choice between human umbilical vein (HUV) or polytetrafluoroethylene (PTFE) when the saphenous vein is inadequate remains unclear. In a multi-centre trial of 801 femoro-popliteal bypasses, autogenous vein could not be used in 252 (31%), of which 191 were randomised to either HUV or PTFE and started on aspirin 300 mg plus dipyridamole 150 mg (ASA + DPM) twice daily. Graft patency measured objectively by independent trial coordinators was expressed on an "intention to treat" basis by life table and analysed statistically by log rank and confidence intervals (95% CI). Overall, 101 grafts failed and cumulative patency was 53% (45-61%) at 3 years compared with 60% (55-65%) in 549 vein grafts. Prosthetic bypass patency above knee was 65% (55-75%); markedly better than 35% (23-47%) below knee (p less than 0.001) and comparable with 62% (55-69%) in 217 above knee saphenous vein grafts. Most failures occurred early at a rate of 52/1000 patient-months in the first 3 months (43/1000 for vein) falling to 21/1000 by 6 to 12 months and around 10/1000 subsequently. Randomisation produced comparable groups of 87 HUV and 104 PTFE grafts. Cumulative primary patency for HUV was 68, 63 and 57% at 1, 2 and 3 years, respectively compared with 61, 56 and 48% for PTFE with wide confidence intervals for the difference at 3 years (-20 to 38%, p = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗

PubMed1991

Dietary fiber in hospitalized geriatric patients: too soft a solution for too hard a problem?

Increased fiber in the diet has been shown in the past to improve bowel function in elderly outpatients and in long-term care institutions. A randomized placebo-controlled, double-blind study was conducted in a geriatric ward of an acute-care hospital to see if a palatable form of fiber would decrease the incidence of constipation and use of laxatives. In this patient sample, no beneficial effect of fiber supplementation could be found when used up to three weeks.

Aged↗

PubMed1991

Outcomes of emergency room treatment of children with asthma.

Duration of symptoms, medication use and follow-up medical care were examined over an 8-week period in children following emergency room treatment for an acute asthma episode. Two groups of children were compared: Short-course (N = 90) and Continuous Medication Users (N = 46). Over a third of Short-Course Users continued to report symptoms up to 6 weeks following the index episode with 31% reporting medication use at 8 weeks. Relapse, resulting in an emergency room visit, occurred in 26% of all study children. Factors associated with relapse included maternal smoking, female gender, prior hospitalization for asthma, cough, and medication use during the follow-up period.

Asthma↗

PubMed1991

Flexion angles of the knee in different resting positions and their relation to the prevalence of osteoarthritis.

The effect of different resting postures on the loading profile of the knee in 1,155 subjects was studied. The recent change to chair sitting has radically modified this profile, resulting in an increase in midflexion loading and virtual disuse of full flexion of knee and hip. Domestic activities do not compensate for this underutilization. There is consistent evidence from 7 communities that the prevalence of osteoarthritis of the hip is substantially lower in communities that do not habitually chair-sit. No other adequate explanation for this difference has been identified. These findings suggest a need to reexamine the incomplete use hypothesis.

Female↗

PubMed1991

Social environment and vulnerability of low birth weight children: a social-epidemiological perspective.

This study examined the impact of low birth weight on children's health and assessed the influence of the social environment on various aspects of health in low birth weight and normal birth weight children. Data on 8661 children aged 2 through 11 from the 1981 Child Health Supplement of the National Health Interview Survey provided strong evidence for two major conclusions: (1) Low birth weight children in high-risk social environments are at increased for poor health outcomes compared with comparable normal birth weight children. This vulnerability was found across all age groups, suggesting that the effects of low birth weight are long-lasting. The poor health outcomes for low birth weight children in high-risk social environments were found for all seven aspects of child health status studied: excessive bed days, restricted-activity days, and school-loss days; school failure, low school-ranking, behavior problems, and maternal perception of child health status as fair/poor. (2) The mechanism of risk was complex and differed by birth weight group. Whereas certain combinations of individual risk factors protected normal birth weight children from several adverse outcomes, none for low birth weight children were identified. However, low birth weight children in low- or moderate-risk social environments were not at greater risk for poor outcomes compared with comparable normal birth weight children. This study underscores the importance of a healthy social environment for children who are already at high risk for poor health outcomes by virtue of being low birth weight.

Age Factors↗

PubMed1991

Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.

To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease.

Aspirin↗

PubMed1990

The influence of smoking and plasma factors on prosthetic graft patency.

The effects of smoking and plasma risk factors on the patency of prosthetic femoro-popliteal bypass grafts were investigated in 93 patients entered into a multicentre trial of prosthetic graft materials (70 patients had patent grafts and 23 patients had occluded grafts 2 years after surgery). The smoking markers thiocyanate and fibrinogen were significantly higher in patients with occluded grafts, whereas LDL-cholesterol was significantly higher in patients with patent grafts 2 years after bypass. Based on smoking markers, graft patency in smokers was 57% at 2 years by life table, compared to 78% in non-smokers. P less than 0.05. Fibrinogen was an important variable, predicting graft occlusion with graft patency in patients with below median fibrinogen levels, being 84% at 2 years by life table compared to 51% in those with above median fibrinogen levels, P less than 0.025. Although increased levels of LDL-cholesterol have been associated with accelerated atherosclerosis, patients with above median levels of LDL-cholesterol had improved graft patency (83%) at 2 years compared to patency in patients with below median LDL-cholesterol (60%), P less than 0.05. The plasma risk factors associated with the failure of prosthetic grafts are similar to those associated with the failure of saphenous vein grafts, indicating that higher fibrinogen levels and smoking may contribute to an hypercoagulable state. Greater efforts are needed to stop patients smoking after vascular reconstruction.

Aged↗

PubMed1990

Filtration as part of the validation and routine testing of a purified water system.

A distillation system, which includes a steam condensate supply, pre-treated before distillation by passage through carbon and mixed resin barrels, is described. Filtration of 5-litre aliquots from a storage tank/ring mains system through a 0.45-micron cellulose filter identified contaminants (rust from the ring mains and carbon from the barrel) which were not detected by the British Pharmacopoeia tests for purified water.

Filtration↗

PubMed1990

Environmental risk factors in Parkinson's disease.

To investigate possible risk factors for Parkinson's disease (PD) we conducted a case-control study of 150 PD patients and 150 age- and sex-matched controls. We interviewed and examined all 300 subjects. We collected demographic data including lifetime histories of places of residence, source of drinking water, and occupations such as farming. Subjects completed a detailed questionnaire regarding herbicide/pesticide exposure. Rural living and drinking well water were significantly increased in the PD patients. This was observed regardless of age at disease onset. Drinking well water was dependent on rural living. There were no significant differences between cases and controls for farming or any measure of exposure to herbicides or pesticides. These data provide further evidence that an environmental toxin could be involved in the etiology of PD.

Aged↗

PubMed1990

[Renal digital angiography in the study of hypertensive patients].

50 patients, 31 male and 19 female with mean age of 45.1 +/- 9.4 years afflicted with blood hypertension (BH) were studied. RDA was performed on all of them as part of the etiological study. The variables evaluated were: systolic blood pressure (SBP), diastolic blood pressure (DBP), therapy index (TI), evolution time of its BH and type of BH (refractory BH, severe BH, mild-moderate BH). The organ affliction was also evaluated (renal function, ECG, presence of cardiomyopathy, vascular disease, and retinopathy. RDA alteration appeared in 16 cases, 1 (10%) in refractory BH group, 8 (28.6%) in severe BH group, and 7 (58.3%) in mild-moderate BH group. A shorter BH evolution period having been observed in patients with altered RDA than in those with normal RDA (3.49 +/- 3.96 years vs 6.93 +/- 4.68 years p = 0.01). We conclude that only this variable is a feature for suspicion of renovascular BH, without an apparent difference between the results of RDA and those of I.V. urography, obtained during the diagnosis screening. The significant differences observed between the mild-moderate BH and the other groups suggests that the clinical suspicion, and not the severity of the BH, is the point which should determine the patients to be renovascularly explored.

Adult↗

PubMed1990

[99mTc-2-methoxy-isobutyl-isonitrile in the diagnosis of coronary heart disease: results of a multicenter study].

A total of 226 patients was studied in a phase-III multicenter trial to compare the results of stress/rest 99mTc-MIBI with 201TI scintigraphy and/or coronary arteriography. The evaluation of planar and SPECT imaging was based on a semiquantitative visual scoring. A congruent diagnosis was generated from all planar 201TI and 99mTc-MIBI scintigrams performed in 36 patients. In 62 of 63 patients, SPECT-studies with 99mTc-MIBI and 201TI led to an identical diagnosis. In one patient a positive result was obtained with 201TI-SPECT whereas 99mTc-MIBI was negative. Segmental agreement for 1509 SPECT segments was 85.7%, for 554 planar segments it was 86.6%. In comparison to coronary arteriography, performed in 180 patients, the overall sensitivity for the correct diagnosis of coronary artery disease (CAD) was 86% for planar MIBI scintigraphy or 92% for MIBI-SPECT. Overall specificity was 100% for planar imaging and 57% for SPECT. The low specificity of MIBI-SPECT was probably due to high prevalence of CAD in this study population. In a subgroup of 43 patients, who underwent coronary angiography, identical results were found with 99mTc-MIBI and 201TI. Only one patient showed a positive scintigraphic result with both 99mTc-MIBI and 201TI without angiographically proven stenosis greater than 50% or prior myocardial infarction. Vessel sensitivities in stenosed coronary arteries (greater than 50% stenosis) were 54% for the LAD and 87% for the RCX/RCA areas with MIBI-SPECT, or 51% or 79% for planar scintigraphy, respectively. Vessel specificities for SPECT were 65% in the LAD or 52% in the RCX/RCA, or 90% or 83% in planar imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗