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Biomedical subjects

L K Johnson

Publications and source records attributed to L K Johnson.

At least 19 recordsLinked to original sources

[Diet and secondary prevention of coronary heart disease--are our recommendations good enough?].

BACKGROUND: Dietary treatment plays an important role in prevention of coronary heart disease. In Norway as in other European countries, patients with established coronary heart disease are advised to follow a cholesterol-lowering diet. However, epidemiological observations have suggested that Mediterranean and other diets may have cardioprotective characteristics beyond their effects on serum total and LDL cholesterol levels. MATERIAL AND METHODS: We describe the results of randomised, controlled clinical trials that have investigated the effect of diet on secondary prevention of coronary heart disease. RESULTS: Diets characterised by high contents of oleic acid (18: 1n-9), alpha-linolenic acid (18: 3n-3) and fish or fish oil and near-vegetarian diets have reduced cardiovascular morbidity and mortality in patients with coronary heart disease. INTERPRETATION: Several characteristics of the Mediterranean diet seem to have additional anti-atherothrombogenic effects beyond those observed with the usually recommended cholesterol-lowering diet. We ask whether Norwegian dietary recommendations for secondary prevention, should emphasise more strongly the type of fat used and fruit and vegetable intake, in line with the principles of the Mediterranean diet. Such dietary advice should be incorporated into the medical treatment given to all patients with coronary heart disease, regardless of their lipid profile.

Coronary Disease↗

Oocyte donor screening: the selection process and cost analysis.

OBJECTIVE: To evaluate the selection process and cost of screening oocyte donors. DESIGN: Retrospective analysis. SETTING: University-based IVF program. PATIENT(S): Potential oocyte donors. INTERVENTION(S): Outcomes of all inquiries by individuals responding to recruitment advertisements for oocyte donors over a 10-month period were assessed. Recruitment and screening costs to bring a single donor into the program were calculated. MAIN OUTCOME MEASURE(S): The attrition rate for each step of the oocyte donor screening process was determined. The costs assessed over the study period included the following: advertisement, administrative, professional, ultrasound, and blood screening. The total cost to bring a single donor into the program was calculated. RESULT(S): Advertisements led to 315 phone inquiries from potential oocyte donors. Of these, a total of 223 (71%) voluntarily withdrew from the screening process, 54 (17%) were screened out for medical or psychological reasons, and 38 (12%) entered the active donor pool. The total cost to bring a single donor into the program was approximately 1,869 dollars. CONCLUSION(S): There was significant attrition in the screening process for oocyte donation that needs to be taken into account in determining the costs of managing the program.

Advertising↗

Granulomatous skin lesions in moray eels caused by a novel Mycobacterium species related to Mycobacterium triplex.

An outbreak of granulomatous dermatitis was investigated in a captive population of moray eels. The affected eels had florid skin nodules concentrated around the head and trunk. Histopathological examination revealed extensive granulomatous inflammation within the dermis and subcutaneous fascial plane between the fat and axial musculature. Acid-fast rods were detected within the smallest lesions, which were presumably the ones that had developed earliest. Eventually, after several months of incubation at room temperature, a very slowly growing acid-fast organism was isolated. Sequencing of the 16S rRNA gene identified it as a Mycobacterium species closely related (0.59% divergence) to M. triplex, an SAV mycobacterium. Intradermal inoculation of healthy green moray eels with this organism reliably reproduced the lesion. Experimentally induced granulomatous dermatitis appeared within 2 weeks of inoculation and slowly but progressively expanded during the 2 months of the experiment. Live organisms were recovered from these lesions at all time points, fulfilling Koch's postulates for this bacterium. In a retrospective study of tissues collected between 1993 and 1999 from five spontaneous disease cases, acid-fast rods were consistently found within lesions, and a nested PCR for the rRNA gene also demonstrated the presence of mycobacteria within affected tissues.

Animals↗

Use of repetitive DNA sequences and the PCR To differentiate Escherichia coli isolates from human and animal sources.

The rep-PCR DNA fingerprint technique, which uses repetitive intergenic DNA sequences, was investigated as a way to differentiate between human and animal sources of fecal pollution. BOX and REP primers were used to generate DNA fingerprints from Escherichia coli strains isolated from human and animal sources (geese, ducks, cows, pigs, chickens, and sheep). Our initial studies revealed that the DNA fingerprints obtained with the BOX primer were more effective for grouping E. coli strains than the DNA fingerprints obtained with REP primers. The BOX primer DNA fingerprints of 154 E. coli isolates were analyzed by using the Jaccard band-matching algorithm. Jackknife analysis of the resulting similarity coefficients revealed that 100% of the chicken and cow isolates and between 78 and 90% of the human, goose, duck, pig, and sheep isolates were assigned to the correct source groups. A dendrogram constructed by using Jaccard similarity coefficients almost completely separated the human isolates from the nonhuman isolates. Multivariate analysis of variance, a form of discriminant analysis, successfully differentiated the isolates and placed them in the appropriate source groups. Taken together, our results indicate that rep-PCR performed with the BOX A1R primer may be a useful and effective tool for rapidly determining sources of fecal pollution.

Animals↗

Chemoprevention of colon cancer carcinogenesis by balsalazide: inhibition of azoxymethane-induced aberrant crypt formation in the rat colon and intestinal tumor formation in the B6-Min/+ mouse.

Non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin have been shown to suppress colon carcinogenesis and in some cases reduce the size of colorectal polyps. Balsalazide disodium (BSZ) is a colon-specific prodrug of the salicylate, 5-aminosalicylic acid. The aim of the present study was to test the chemopreventive activity of BSZ in two established animal models of colon tumorigenesis, azoxymethane-induced aberrant crypt formation in the rat and intestinal tumor formation in the B6-Min/+ mouse. Aberrant crypt foci (ACF) were induced in Fischer 344 rats via 2 subcutaneous injections of azoxymethane (20 mg/kg). BSZ was supplied in the drinking water for 8 weeks and ACF quantitated. B6-Min/+ mice were treated from 55 days of age for 90 days and intestinal tumors scored for number, size and location. BSZ treatment of AOM-injected rats reduced ACF formation in a dose-dependent manner by 60% with the greatest effect observed on ACF with 4 or more crypts. In B6-Min/+ mice a dose-dependent reduction of intestinal tumor number was observed which reached 80% in the distal small intestine and colon. A preliminary mechanistic study in cultured human colon cancer cells showed that both BSZ and 5-ASA inhibited colon cancer cell proliferation in vitro. However, 5-ASA but not BSZ produced changes consistent with the induction of apoptosis. BSZ produces a dose-dependent chemopreventive effect on colon carcinogenesis. A possible mechanism is consistent with the inhibition of cellular proliferation and the induction of apoptosis.

Aminosalicylic Acids↗

Dietary copper primarily affects antioxidant capacity and dietary iron mainly affects iron status in a surface response study of female rats fed varying concentrations of iron, zinc and copper.

This study was designed to examine the interactions among dietary iron (Fe), copper (Cu), and zinc (Zn) and their effects on Fe status and oxidative stress in female rats. In a three-factor central composite response surface design, rats were assigned to 15 groups and fed modified AIN-93G basal diets with varying amounts of Fe and Zn (7.0, 15.5, 45.8, 135.6, or 300 micrograms/g diet) and Cu (0.5, 1.1, 3.2, 9.2, or 20 micrograms/g diet) for 6 wk. Variations in hemoglobin, hematocrit, and serum ferritin were mainly related to dietary Fe. Liver nonheme Fe was directly affected by dietary Fe and was slightly attenuated by interactions between Cu and Zn, and Zn and Fe. Serum ceruloplasmin activity was primarily determined by an interaction between Cu and Zn with substantial moderation by the quadratic effect of dietary Cu. Liver and heart total superoxide dismutase (SOD) and Cu/Zn SOD activities were directly affected by dietary Cu. Dietary Fe was the only significant, yet weak, predictor of liver thiobarbituric acid reactive substances (TBARS) and vitamin E content and serum triacylglycerols. Variability in serum Cu was mostly determined by the interaction between Cu and Fe, with modification from the quadratic effect of dietary Cu. Serum Zn varied with dietary Zn with a small negative influence from the interaction between Cu and Fe. In summary, Fe status was minimally influenced by dietary Zn or Cu, and Fe intakes 10-fold greater than required did not induce overt oxidative stress in female rats. In addition, measures of antioxidant capacity were primarily influenced by dietary Cu and were optimal at moderate intakes of this micronutrient.

Animals↗

Zinc absorption, mineral balance, and blood lipids in women consuming controlled lactoovovegetarian and omnivorous diets for 8 wk.

Zinc absorption, mineral balance, and blood lipid concentrations were measured in 21 women aged 33 +/- 7 y (range: 20-42 y) consuming controlled lactoovovegetarian and nonvegetarian diets for 8 wk each in a crossover design. The lactoovovegetarian and nonvegetarian diets, respectively, provided (by analysis) 973 and 995 mg Ca, 1.8 and 1.3 mg Cu, 367 and 260 mg Mg, 5.9 and 2.5 mg Mn, 1457 and 1667 mg P, 9.1 and 11.1 mg Zn, and (by calculation) 40 and 16 g dietary fiber, 2.5 and 0.8 mmol phytic acid, molar ratios of phytate to Zn of 14 and 5, and millimolar ratios of (phytate x Ca) to Zn of 344 and 111. Dietary zinc absorption was measured by extrinsic isotopic labeling and whole-body counting. Plasma cholesterol, cholesterol fractions, and lipoproteins were reduced 7-12% with the lactoovovegetarian diet, consistent with predictions based on dietary cholesterol and fat. Blood pressure was unaffected. Calcium, copper, magnesium, and phosphorus balances were not different between diets; manganese balance tended to be greater with the lactoovovegetarian diet (P < 0.07). The lactoovovegetarian diet was associated with a 21% reduction in absorptive efficiency that, together with a 14% reduction in dietary zinc, reduced the amount of zinc absorbed by 35% (2.4 compared with 3.7 mg/d) and reduced plasma zinc by 5% within the normal range. Zinc balance was maintained with both diets. Although there is a greater risk of zinc deficiency in persons consuming lactoovovegetarian compared with omnivorous diets, with inclusion of whole grains and legumes zinc requirements can be met and zinc balance maintained.

Adult↗

Effect of age and caloric restriction on cutaneous wound closure in rats and monkeys.

Cutaneous wounds close more slowly in rats and monkeys as age increases. Caloric restriction of 40% in rats and 30% in monkeys did not significantly affect healing rates, although it did exert a trend toward faster closure. Similarly, voluntary exercise did not significantly alter healing rates in rats. Thus, impaired wound healing appears to be a generalized physiological manifestation of aging, but its possible amelioration by "anti-aging" interventions remains to be established.

Aging↗

Endocrine neoplasia in New World primates.

Of 1,106 New World primates necropsied from the National Zoological Park (Washington, D.C.) and the Department of Comparative Pathology, Johns Hopkins University School of Medicine (Baltimore, Maryland) 22 (1.9%) animals were identified with 27 neoplasms. Of this group, nine animals (two females, seven males) had a total of 13 endocrine neoplasms. All animals were adults, with an age range of 2.7-25 years (average, 12.1 years). Seven were Callitrichidae and two were Cebidae. The adrenal gland was the most affected organ, with seven (53.8%) neoplasms, followed by the pituitary and thyroid gland with two (15.4%) cases each, and the pancreas and parathyroid gland with one tumor (7.7%) each. All neoplastic disorders were benign. Immunocytochemistry assays for growth hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and chromogranin A were performed on two pituitary neoplasms. Pheochromocytoma was the most frequent neoplasm, representing 5 (38.4%) of the 13 neoplasms. The remaining were thyroid cystadenoma (two, 15.4%), corticotrophic cell pituitary adenoma (two, 15.4%), adrenal ganglioneuroma (one, 7.7%), adrenal cortical adenoma (one, 7.7%), parathyroid chief-cell adenoma (one, 7.7%), and pancreatic islet-cell adenoma (one, 7.7%).

Adenoma↗

Structure of the human urokinase receptor gene and its similarity to CD59 and the Ly-6 family.

Urokinase plasminogen activator receptor (uPAR) gene expression has been implicated in many important biological processes including cell invasiveness and migration. The uPAR gene was cloned from a human genomic library by hybridization with a uPAR cDNA. The complete structure of the human uPAR gene, including a 21.23-kb transcription unit with 204 bp 5' and 239 bp 3' flanking sequences, was determined by comparison with the uPAR cDNA sequence. The uPAR gene is composed of seven exons and six introns. The seven exons of 101, 111, 144, 162, 135, 147 and 563 bp are separated by six introns of approximately 2.04, 2.62, 8.42, 0.906, 3.10 and 2.78 kb. Exons 1-7 encode 19, 37, 48, 54, 45, 49 and 83 amino acid residues, respectively. A CpG-rich island and sequences related to the transcription factors AP-1, AP-2, c-Jun and NF kappa B are present, but no potential TATA or CAAT boxes were found in the proximal 5' region of the uPAR gene. Comparison of the exon organization of the uPAR gene with that of human CD59 and murine Ly-6 reveals similarity to all three domains encoded by the uPAR exons (2 + 3), (4 + 5) and (6 + 7). These data enable elucidation of the mechanisms involved in regulation of the uPAR gene expression and provide further evidence that the uPAR gene belongs to the Ly-6 superfamily.

Amino Acid Sequence↗

High- versus low-meat diets: effects on zinc absorption, iron status, and calcium, copper, iron, magnesium, manganese, nitrogen, phosphorus, and zinc balance in postmenopausal women.

The effects of three diets--high meat (HM), low meat (LM), or low meat with mineral supplements (LS)--on zinc absorption, elemental balance, and related clinical indexes were investigated in a metabolic study of 14 women aged 51-70 y. The women ate each of the three diets for 7 wk in random order. Lean beef, chicken, ham, and tuna in the HM diet replaced foods with a low mineral content in the LM diet. The LS diet was similar to the HM diet in K, P, Fe, Mg, and Zn contents. Compared with the other diets, the HM diet increased zinc absorption and retention, and slightly increased urinary zinc. Nitrogen and calcium balances and urinary calcium were not different for the HM and LM diets. Iron balance was not different for the HM and LS diets with similar iron content, but the HM diet was unexpectedly associated with lower iron status (higher iron-binding capacity and lower ferritin than LM and LS diets). These results indicate that 0.8 g protein/kg body wt meets protein requirements in older women, and that high meat consumption increases zinc retention without compromising calcium status and may reduce indexes of iron status, in contrast with iron absorption results from studies with radiolabeled test meals.

Absorption↗

Severe or marginal iron deficiency affects spontaneous physical activity in rats.

The influence of dietary iron on spontaneous activity was investigated in growing rats. Male rats weighing 97 +/- 10 g fed diets containing 4.6 (deficient), 19.9 (marginal), and 108.4 (adequate) mg Fe/kg diet for 8 wks had hemoglobin values of 52 +/- 6, 152 +/- 4, and 159 +/- 6 g/L, and liver nonheme iron concentrations of 0.79 +/- 0.24, 1.36 +/- 0.39, and 4.58 +/- 0.62 mumol/g, respectively. Body weights were affected only at the lowest iron intake. Diurnal activity was not reversed by iron status; all animals were more active during the dark cycle than the light cycle. Iron deficiency resulted in less time and frequency of horizontal, vertical, and stereotypic movements; less distance moved; and less frequent rotations. Movement speed of iron-deficient rats was faster during early iron deficiency. In the light, rats with marginal iron nutriture were generally more active than were iron-deficient or iron-adequate animals. In the dark, activity generally decreased with each reduction in dietary iron.

Analysis of Variance↗

Effect of ascorbic acid on apparent iron absorption by women with low iron stores.

The effect of ascorbic acid supplementation on apparent iron absorption was tested in women with low iron stores. For 10 wk, 25 healthy nonpregnant women, aged 20-45 y with low serum ferritin (3.5-17.7 micrograms/L), consumed either a diet with predicted poorly bioavailable iron or a typical Western diet, classified according to dietary meat and ascorbic acid contents. Meals were supplemented with ascorbic acid (500 mg, three times a day) for 5 of the 10 wk, in a double-blind, crossover design. Ascorbic acid did not affect most biochemical indexes of iron status, the biological half-life of 59Fe, or apparent iron absorption (diet-feces) from either diet, but slightly increased serum ferritin (11.9 vs 10.7 micrograms/L, P < 0.06) when data from both diets were combined. These results support other evidence that ascorbic acid has less effect on iron bioavailability than has been predicted from tests with single meals.

Adult↗

Sex affects manganese absorption and retention by humans from a diet adequate in manganese.

Men (n = 20) and women (n = 20) consuming a diet adequate in manganese were fed 0.037 mBq 54Mn in a test meal. Subjects were counted in a whole-body counter for 70 d to determine whole-body retention of 54Mn. Data from days 10 to 20 and from days 19 to 70 were analyzed by linear regression to calculate absorption and biological half-life. Men absorbed significantly less 54Mn than women, but the 54Mn absorbed had a longer half-life in men. Estimates of absorption were higher, and estimates of half-life were lower, when data from days 10 to 20 were used compared with days 19 to 70. There was a significant association between manganese absorption and plasma ferritin concentrations and between manganese absorption and biological half-life. We conclude that men and women differ in manganese metabolism and that such differences may be related to iron status. We also conclude that regression estimates of absorption determined by using whole-body retention curves depend on the portion of the data used.

Adolescent↗

Aging of a class of arteries in various mammalian species in relation to the life span.

Age-related sclerosis of human renocortical arteries is associated with essential hypertension and limitation of the life span by cardiovascular mortality. Arteries in the kidneys of nonprimate species, examined here, showed near absence of arteriosclerosis when the average life span was less than 12 years and small amounts of sclerosis in longer-lived species. The fastest progression of arteriosclerosis was, paradoxically, in the longest-lived species, the human and the macaque. Results are incompatible with theories of aging that include arteriosclerosis within the framework of mechanisms that are proposed to explain the life spans of species.

Adolescent↗