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Biomedical subjects

N Mann

Publications and source records attributed to N Mann.

At least 19 recordsLinked to original sources

Recombinant expression analysis of natural and synthetic bovine alpha-casein in Escherichia coli.

As a prelude to developing a yeast-based fermentation process for the production of phenylalanine-free alpha-casein as a foodstuff for patients suffering from phenylketonuria, we cloned the gene encoding bovine alpha-casein. We synthesised a modified gene sequence encoding the same, but devoid of phenylalanine codons and with a codon bias similar to that of naturally occurring highly expressed genes in Saccharomyces cerevisiae. The results show that both gene sequences are readily expressed in Escherichia coli when cloned in an E. coli bacteriophage T7 promoter-driven plasmid vector. In this host, the natural and synthetic casein proteins were produced at levels equating to 18.0% and 7.6% of the cell's soluble protein, respectively.

Amino Acid Sequence↗

Dietary lean red meat and human evolution.

Scientific evidence is accumulating that meat itself is not a risk factor for Western lifestyle diseases such as cardiovascular disease, but rather the risk stems from the excessive fat and particularly saturated fat associated with the meat of modern domesticated animals. In our own studies, we have shown evidence that diets high in lean red meat can actually lower plasma cholesterol, contribute significantly to tissue omega-3 fatty acid and provide a good source of iron, zinc and vitamin B12. A study of human and pre-human diet history shows that for a period of at least 2 million years the human ancestral line had been consuming increasing quantities of meat. During that time, evolutionary selection was in action, adapting our genetic make up and hence our physiological features to a diet high in lean meat. This meat was wild game meat, low in total and saturated fat and relatively rich in polyunsaturated fatty acids (PUFA). The evidence presented in this review looks at various lines of study which indicate the reliance on meat intake as a major energy source by pre-agricultural humans. The distinct fields briefly reviewed include: fossil isotope studies, human gut morphology, human encephalisation and energy requirements, optimal foraging theory, insulin resistance and studies on hunter-gatherer societies. In conclusion, lean meat is a healthy and beneficial component of any well-balanced diet as long as it is fat trimmed and consumed as part of a varied diet.

Adaptation, Biological↗

Sitting balance following brain injury: does it predict outcome?

Balance dysfunction is commonly observed following traumatic brain injury. There are many proposed predictors of functional outcome in the traumatic brain injury population. It was hypothesized that the degree of balance dysfunction on admission to rehabilitation would be a significant predictor of the need for assistance at discharge, as measured by the Functional Independence Measure (FIM). This study involved 237 cases of traumatic brain injury patients admitted to a rehabilitation unit between November 1989 and September 1996. Using a multiple regression model, controlling for age, initial Glasgow Coma Score (GCS), rehabilitation admission strength, sitting balance and standing balance, it was found that the degree of impairment in sitting balance at admission to rehabilitation was a significant predictor of Discharge FIM-Total (FIM-T) score (p < 0.0001) and also of selected elements from the Discharge FIM-Motor (FIM-M) score (p < 0.0005). The combination of age, initial admission GCS, rehabilitation admission strength, standing balance and sitting balance accounted for 29% of the variance in the Discharge Total FIM score. Among these, sitting balance was the second most powerful predictor of both selected elements of the Discharge FIM motor score and discharge FIM-T. Sitting balance predictive capacity was exceeded in power only by age. Impairments in sitting balance appear to have a significant impact on functional outcome. Emphasis on unique rehabilitation techniques to treat balance dysfunction in the adult TBI population is warranted.

Activities of Daily Living↗

Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets.

Both anthropologists and nutritionists have long recognized that the diets of modern-day hunter-gatherers may represent a reference standard for modern human nutrition and a model for defense against certain diseases of affluence. Because the hunter-gatherer way of life is now probably extinct in its purely un-Westernized form, nutritionists and anthropologists must rely on indirect procedures to reconstruct the traditional diet of preagricultural humans. In this analysis, we incorporate the most recent ethnographic compilation of plant-to-animal economic subsistence patterns of hunter-gatherers to estimate likely dietary macronutrient intakes (% of energy) for environmentally diverse hunter-gatherer populations. Furthermore, we show how differences in the percentage of body fat in prey animals would alter protein intakes in hunter-gatherers and how a maximal protein ceiling influences the selection of other macronutrients. Our analysis showed that whenever and wherever it was ecologically possible, hunter-gatherers consumed high amounts (45-65% of energy) of animal food. Most (73%) of the worldwide hunter-gatherer societies derived >50% (> or =56-65% of energy) of their subsistence from animal foods, whereas only 14% of these societies derived >50% (> or =56-65% of energy) of their subsistence from gathered plant foods. This high reliance on animal-based foods coupled with the relatively low carbohydrate content of wild plant foods produces universally characteristic macronutrient consumption ratios in which protein is elevated (19-35% of energy) at the expense of carbohydrates (22-40% of energy).

Agriculture↗

The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters.

OBJECTIVE: The aim of this study was to assess thrombosis tendency in subjects who were habitual meat-eaters compared with those who were habitual vegetarians. DESIGN: Cross-sectional comparison of habitual meat-eaters and habitual vegetarians. SETTING: Free living subjects. SUBJECTS: One hundred and thirty-nine healthy male subjects (vegans n = 18, ovolacto vegetarians n = 43, moderate-meat-eaters n = 60 and high-meat-eaters n = 18) aged 20-55 y who were recruited in Melbourne. OUTCOME MEASURES: Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. The parameters of thrombosis were measured by standard methods. RESULTS: Saturated fat and cholesterol intakes were significantly higher and polyunsaturated fat (PUFA) was significantly lower in the meat-eaters compared with vegetarians. In the meat-eaters, the platelet phospholipids AA levels were significantly higher than in the vegetarians, but there was no increase in ex vivo platelet aggregation and plasma 11-dehydro thromboxane B2 levels. Vegetarians, especially the vegans, had a significantly increased mean collagen and ADP stimulated ex vivo whole blood platelet aggregation compared with meat-eaters. The vegan group had a significantly higher mean platelet volume than the other three dietary groups. However, meat-eaters had a significantly higher cluster of cardiovascular risk factors compared with vegetarians, including increased body mass index, waist to hip ratio, plasma total cholesterol (TC), triacylglycerol and LDL-C levels, ratio of TC/HDL-C and LDL-C/HDL-C and plasma factor VII activity. CONCLUSIONS: Consumption of meat is not associated with an increased platelet aggregation compared with vegetarian subjects.

Adult↗

Does the requirement of a craniotomy predict outcome? A preliminary investigation.

The literature has been replete with reports that persons who require craniotomy for treatment of their traumatic brain injury have a far worse outcome. The majority of these reports have utilized the rather global Glasgow Outcome Scale as a determinant of outcome. This paper sought to evaluate the effect of craniotomy on outcome as measured by the DRS. Data was collected on 341 persons (mean age 37.7 years) with traumatic brain injury treated at the Level I trauma centre, who required inpatient rehabilitation. Surgical interventions were classified as 'no surgery', 'one cranial surgery', or 'two or more cranial surgeries'. Initial GCS scores revealed 44 persons at GCS 3-5, 102 persons at GCS 6-8, 83 persons at GCS 9-12 and 112 persons at GCS 13-15. The DRS was administered to each person at discharge from in-patient rehabilitation. Mean DRS scores were 7.07 for GCS 3-5, 6.03 for GCS 6-8, 6.53 for GCS 9-12, 5.57 for GCS 13-15 groups. A factorial ANOVA revealed an interaction between initial GCS and surgical status. Univariate ANOVA's demonstrated significant differences in the GCS 3-5 and GCS 13-15 groups, suggesting a relationship between need for surgical intervention and less favourable outcome among persons who required in-patient rehabilitation. However, no differences were demonstrated in the GCS 6-8 and GCS 9-12 groups. It appears that requiring surgical intervention is prognostic at only the extremes of the GCS categories and, thus, further investigation may reveal the limited role of need for surgical intervention injury in predicting outcome in persons with initial GCS 6-12.

Activities of Daily Living↗

Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men.

BACKGROUND: Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. OBJECTIVE: We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. DESIGN: During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. RESULTS: Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. CONCLUSION: ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males.

Adult↗

Transition metals as protease inhibitors.

An alternative approach to the development of clinically useful protease inhibitors was investigated. The approach utilized coordination chemistry of transition metal ions rather than substrate analogs to block active sites of these enzymes. In the case of serine proteases it was found that aqueous Ti(IV) is a potent inhibitor of the trypsin subclass, but not the chymotrypsin subclass. The direct binding of Ti(IV) to trypsin was made possible by the presence of a free carboxyl group at the bottom of the substrate binding pocket of the enzyme, and the five-coordinate geometry of TiO(SO4)(H2O). Although initial binding of Ti(IV) was reversible, it was followed in time by irreversible inhibition. Direct binding of octahedral or tetrahedral metal ion complexes was prevented by the inability of the enzyme active sites to promote formation of a five-coordinate transition state of the metal ion required for reaction. These studies demonstrate the ability of direct metal ion binding as a way to enhance blocking of enzyme active sites as compared with that of traditional organic inhibitors. Application of these findings was investigated by measuring the affect Ti(IV) had on growth of Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa. Five-coordinate titanyl sulfate completely inhibited the growth of these organisms. This suggests that five-coordinate titanyl sulfate, which is easier and less expensive to manufacture than conventional antibiotics, may be useful in controlling endemic infections of E. coli and S. typhimurium.

Binding Sites↗

Brain injury as a result of violence: preliminary findings from the traumatic brain injury model systems.

OBJECTIVES: To identify possible risk factors that may predispose individuals to violent traumatic brain injury (TBI) and to determine the effect of etiology of injury on outcomes. STUDY DESIGN: Prospective, longitudinal multicenter study. SETTING: TBI Model Systems (TBIMS) located at Wayne State University/Rehabilitation Institute of Michigan, Detroit, MI; The Institute for Rehabilitation and Research, Houston, TX; Medical College of Virginia, Richmond, VA; and Santa Clara Valley Medical Center, San Jose, CA. SUBJECTS: Individuals treated in the four TBIMS programs between 3/89 and 9/96 who met the criteria for inclusion in the TBIMS National Database and for whom the etiology was known (n=812). MAIN OUTCOME MEASURES: Functional Independence Measure, Alcohol Quantity Frequency Variability Index, Community Integration Questionnaire. RESULTS: Individuals who incur violence-related TBI tend to be male, nonwhite, unmarried, living alone, less educated, and unemployed at time of injury. They tend to have less severe brain injuries and better motor function at the time of admission to inpatient rehabilitation. At 1 year postinjury, they score lower on community integration measures; however, no difference exists in functional status. Etiology of injury was found to only play a minor role in the prediction of social and productive integration at 1 year postinjury. CONCLUSIONS: Survivors of violent and nonviolent TBI have similar functional outcomes; however, they differ in preinjury and postinjury socio-economic characteristics, injury severity, and postinjury community integration. Socio-economic factors appear to play a large role in the risk for violent injury and in community integration following injury.

Activities of Daily Living↗

Pulmonary agenesis: a predictor of ipsilateral malformations.

Pulmonary agenesis is a rare malformation that can be isolated or associated with other anomalies. We became interested in pulmonary agenesis after evaluation of a child with right pulmonary agenesis, an unlobed left lung, bilateral cleft lip and palate, maxillary and mandibular hypoplasia, bilateral microtia, bilateral radial ray hypoplasia, horseshoe kidney, and complex congenital heart disease. A review of the occurrence of pulmonary agenesis with other congenital anomalies uncovered a striking association with ipsilateral radial ray defects and/or hemifacial microsomia. The presence of bilateral facial or radial ray anomalies was indicative of bilateral pulmonary involvement. A review of the cases of pulmonary agenesis and associated anomalies at the Children's Hospital and Medical Center confirmed the association of pulmonary agenesis and ipsilateral involvement of face and/or radial ray. The association of pulmonary agenesis and ipsilateral malformations may shed light on its pathogenesis. Although the cause of these associated anomalies remains unclear, abnormalities in the development of the aortic arches during embryogenesis is an attractive hypothesis.

Abnormalities, Multiple↗

The effect of short-term diets rich in fish, red meat, or white meat on thromboxane and prostacyclin synthesis in humans.

Foods which increase tissue arachidonic acid levels have been proposed to increase thrombosis tendency, presumably through increased platelet aggregation. This study examined the effect of doubling the dietary arachidonic acid (20:4n-6) using meat- or fish-based diets on the systemic production of prostacyclin (PGI2) and thromboxane (TXA2) in 29 healthy, nonsmoking adults. There were three, 3-wk low-fat dietary periods (< 15% energy as fat) in which subjects consumed a vegetarian diet for 1 wk followed by 2 wk on diets containing meat or fish as sources of 20:4n-6. Between each diet period, there was a 3-wk washout period, during which subjects returned to their normal diets. The level of 20:4n-6 consumed during the last 2 wk of each study was approximately double the usual intake (mean 140 mg/d), while the mean eicosapentaenoic acid (20:5n-3) content of the diets varied from 1 mg/d on the white meat diet to 70 mg/d on the red meat diet and to 847 mg/d on the fish diet. The serum phospholipid (PL) 20:4n-6/20:5n-3 ratios were 11:1 on the vegetarian diet, 15:1 on the white meat diet, 8:1 on the red meat diet, and 2:1 on the fish diet (P < 0.001). Neither white nor red meat diets affected platelet 20:4n-6 levels, platelet aggregation, ex vivo platelet TXB2 production, or the systemic PGI2 or TXA2 production as measured by gas chromatography-mass spectrometry analysis of the excretion levels of the principal urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and 11-dehydro-TXB2 (TXA2-M), respectively. The fish diet decreased the 20:4n-6/20:5n-3 ratio in platelet PL from the baseline level of 45:1 to 13:1 (P < 0.001), had no effects on platelet aggregation, but significantly decreased platelet TXB2 production (collagen-stimulated) and TXA2-M production, while PGI2-M levels were unaltered. These results indicate that short-term diets which double the usual 20:4n-6 intake using white meat (175-330 g/d) or red meat (275-530 g/d) are not associated with an increased TXA2 production, but this does not rule out the adverse effects of 20:4n-6 at higher levels in the diet, or for more prolonged periods. Short-term diets containing fish (100-200 g/d with 90-210 mg/d 20:4n-6 and approximately 650-1000 mg/d 20:5n-3) led to significant increases in platelet 20:5n-3 levels and a decrease in the ex vivo and systemic TXA2 production.

Adult↗

Telecommunications role evolves beyond mere utility.

A more regionalized healthcare delivery system has expanded the role of the telecommunications department. Applications such as teleradiology and telemedicine are making increasingly sophisticated demands on communications systems and their managers.

Hospital Administration↗

Engineered immunoglobulin molecules as vehicles for T cell epitopes.

The variable regions (V) of immunoglobulins (Ig) bear antigenic determinants that can stimulate both humoral and cellular immune responses subsequent to hetero, allo or iso-immunization. The expression of these determinants by Igs usually correlates with the presence of specific amino acid residues within the CDR loops of the V regions. Since the CDR loops varies in length, we reasoned that they would represent permissive sites to insert foreign peptides and create antigenized Igs expressing selected determinants. Taking advantage of these properties and the fact that Igs are self and long-lived molecules, we expressed a CTL and a helper epitope of influenza virus nucleoprotein and hemagglutinin respectively, within the heavy chain CDR3 loop of an anti-arsonate antibody. We found that foreign peptides comprised of 11 to 15 amino acid residues can be expressed within the V region of the heavy chain without alteration of pairing with the light chain. More striking, the cellular processing machinery is able to generate the peptides from the Ig context which were then recognized by specific T cells. Furthermore, the engineered Igs are able to induce T cell responses specific for the inserted peptide and for influenza virus. The use of engineered Ig molecules as vehicles for T and B cell peptides might represent a valuable strategy to generate safe, long lived reagents able to stimulate strong specific immune responses. This would then overcome the short half life of synthetic peptides based vaccines and the side effects seen in case of recombinant viral proteins or inactivated viruses based vaccines.

Animals↗

Pig disease name.

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Abortion, Veterinary↗