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Biomedical subjects

J Christopher

Publications and source records attributed to J Christopher.

At least 19 recordsLinked to original sources

Sensory and physical properties of peanut brittle prepared in different types of cookware and with different levels of sodium bicarbonate.

Two studies to evaluate peanut brittle containing either raw or roasted peanuts were conducted. In the first study, brittles were prepared in iron, aluminum, stainless steel and nonstick stainless steel pans. In the second study, brittles containing 0, 2 or 4 g of sodium bicarbonate prepared in either stainless steel or nonstick stainless steel pans were evaluated. All brittles were evaluated for color, shear strength and sensory properties at 0, 30 and 60 days. Products prepared in a nonstick stainless steel pan and those with added sodium bicarbonate were lighter, more yellow and slightly greener than other products. Pan type did not affect shear force but increasing sodium bicarbonate was associated with decreasing force needed to shear brittles. Peanut and caramel aromas were not affected by pan type or sodium bicarbonate level but were greater (p < 0.05) in products containing roasted peanuts. Burned flavors were more prevalent in products prepared in iron or stainless steel pans with roasted peanuts. More intense sweet and buttery flavors were detected as level of sodium bicarbonate increased.

Arachis↗

Synthesis and analysis of potent, more lipophilic derivatives of the bradykinin B2 receptor antagonist peptide Hoe 140.

Bradykinin (BK) is an endogenous peptide that has been implicated in several pathological conditions, hence antagonists of its activity have therapeutic potential. The decapeptide Hoe 140 is currently one of the best BK antagonists, but interest remains in finding even more potent compounds. A library of Hoe 140 derivatives was synthesized that incorporated non-natural analogs of the cationic, naturally occurring amino acids arginine (Arg) and lysine (Lys). The modified amino acids were designed to form enhanced ionic interactions due to an increase in local hydrophobicity, which promotes desolvation of the cation in water. The potencies of the resulting peptides were determined by competitive binding assays in human A431 cells expressing the BK B2 receptor. Two of the peptides synthesized were equipotent to Hoe 140 (IC(50s) 2.99 and 3.36 nM) and the most potent was demonstrated as a functional antagonist in vitro by blocking BK-mediated phosphorylation of mitogen-activated protein (MAP) kinases. The new derivatives are more hydrophobic than Hoe 140 and thus may exhibit changes in pharmacokinetic properties when evaluated in vivo.

Arginine↗

Regulation of B(2)-kinin receptors by glucose in vascular smooth muscle cells.

The development of vascular disease is accelerated in hyperglycemic states. Vascular injury plays a pivotal role in the progression of atherosclerotic vascular disease in diabetes, which is characterized by increased vascular smooth muscle cell (VSMC) proliferation and extracellular matrix accumulation. We previously reported that diabetes alters the activity of the kallikrein-kinin system and results in the upregulation of kinin receptors in the vessel wall. To determine whether glucose can directly influence the regulation of kinin receptors, the independent effect of high glucose (25 mM) on B(2)-kinin receptors (B2KR) in VSMC was examined. A threefold increase in B2KR protein levels and a 40% increase in B2KR surface receptors were observed after treatment with high glucose after 24 h. The mRNA levels of B2KR were also significantly increased by high glucose as early as 4 h later. To elucidate the cellular mechanisms by which glucose regulates B2KR, we examined the role of protein kinase C (PKC). High glucose increased total PKC activity and resulted in the translocation of conventional PKC isoforms (beta(1) and beta(2)), novel (epsilon), and atypical (zeta) PKC isoforms into the membrane. Inhibition of PKC activity prevented the increase in B2KR levels induced by ambient high glucose. These findings provide the first evidence that glucose regulates the expression of B(2) receptors in VSMC and provide a rationale to further study the interaction between glucose and kinins on the pathogenesis of atherosclerotic vascular disease in diabetes.

Animals↗

Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells.

A high concentration of circulating low-density lipoproteins (LDL) is a major risk factor for atherosclerosis. Native LDL and LDL modified by glycation and/or oxidation are increased in diabetic individuals. LDL directly stimulate vascular smooth muscle cell (VSMC) proliferation; however, the mechanisms remain undefined. The extracellular signal-regulated kinase (ERK) pathway mediates changes in cell function and growth. Therefore, we examined the cellular effects of native and modified LDL on ERK phosphorylation in VSMC. Addition of native, mildly modified (oxidized, glycated, glycoxidized) and highly modified (highly oxidized, highly glycoxidized) LDL at 25 microg/ml to rat VSMC for 5 min induced a fivefold increase in ERK phosphorylation. To elucidate the signal transduction pathway by which LDL phosphorylate ERK, we examined the roles of the Ca(2+)/calmodulin pathway, protein kinase C (PKC), src kinase, and mitogen-activated protein kinase kinase (MEK). Treatment of VSMC with the intracellular Ca(2+) chelator EGTA-AM (50 micromol/l) significantly increased ERK phosphorylation induced by native and mildly modified LDL, whereas chelation of extracellular Ca(2+) by EGTA (3 mmol/l) significantly reduced LDL-induced ERK phosphorylation. The calmodulin inhibitor N-(6-aminohexyl)-1-naphthalenesulfonamide (40 micromol/l) significantly decreased ERK phosphorylation induced by all types of LDL. Downregulation of PKC with phorbol myristate acetate (5 micromol/l) markedly reduced LDL-induced ERK phosphorylation. Pretreatment of VSMC with a cell-permeable MEK inhibitor (PD-98059, 40 micromol/l) significantly decreased ERK phosphorylation in response to native and modified LDL. These findings indicate that native and mildly and highly modified LDL utilize similar signaling pathways to phosphorylate ERK and implicate a role for Ca(2+)/calmodulin, PKC, and MEK. These results suggest a potential link between modified LDL, vascular function, and the development of atherosclerosis in diabetes.

Animals↗

Induction of B(1)-kinin receptors in vascular smooth muscle cells: cellular mechanisms of map kinase activation.

Vascular smooth muscle cell (VSMC) proliferation is a prominent feature of the atherosclerotic process that occurs after endothelial injury. Although a vascular wall kallikrein-kinin system has been described, its contribution to vascular disease remains undefined. Because the B(1)-kinin receptor subtype (B1KR) is induced in VSMCs only in response to injury, we hypothesize that this receptor may be mediating critical events in the progression of vascular disease. In the present study, we provide evidence that des-Arg(9)-bradykinin (dABK) (10(-8) M), acting through B1KR, stimulates the phosphorylation of mitogen-activated protein kinase (MAPK) (p42(mapk) and p44(mapk)). Activation of MAPK by dABK is mediated via a cholera toxin-sensitive pathway and appears to involve protein kinase C, Src kinase, and MAPK kinase. These findings demonstrate that the activation of B1KR in VSMCs leads to the generation of second messengers that converge to activate MAPK and provide a rationale to investigate the mitogenic actions of dABK in vascular injury.

Animals↗

Should body size preference be a target of health promotion efforts to address the epidemic of obesity in Afro-Caribbean women?

OBJECTIVE: To determine if 1) Afro-Caribbean women prefer large body sizes, 2) the body size preference of Afro-Caribbean men and women are associated, 3) women's preferences are associated with increased risk of obesity or with weight management behaviors. DESIGN: Population samples of 314 and 487 women, ages 20-55 years, were recruited on Barbados and Dominica with response rates of 74% and 77%, respectively. Body size preferences, stress related variables, and demographic data were ascertained by questionnaire. Height and weight were also measured. On Barbados, body preference data were collected from male partners of participants, and data on intentions to perform weight management behaviors were collected from 175 women. RESULTS: Most women preferred body sizes within normal limits, although women on Dominica had a slightly larger ideal body size (IBS) than did Barbadian women (P<.05). On both islands, the size that women thought men preferred was related to their IBS (P<.0001). Likewise, IBS was associated with increased odds of being overweight (P<.001), however most overweight women (>75%) wanted to be smaller. IBS was not related to the intention to exercise or to eat high fat foods. CONCLUSIONS: It is unlikely that body size preference poses a barrier to intervention efforts to reduce the prevalence of overweight in Afro-Caribbean women.

Adult↗

Age-related marrow conversion in the proximal metaphysis of the femur: evaluation with T1-weighted MR imaging.

PURPOSE: To determine the normal chronologic changes in fatty marrow conversion of the proximal femoral metaphysis at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The "marrow conversion index," (signal intensity of the proximal femoral metaphysis divided by signal intensity of the greater trochanter) x 100, was measured in 182 hips of 91 patients who had no evidence of osteonecrosis or diseases involving bone marrow, no history of steroid treatment, and no other risk factors for osteonecrosis. The results were evaluated according to patient age and sex. RESULTS: The index showed a progressive linear increase with age regardless of sex. The index was 65.4% +/- 5.6 (standard deviation) in patients aged 15-19 years and increased monotonously with age to 87.5% +/- 7.0 in patients aged 60-79 years. Simple linear regression of the index according to age group showed that the marrow conversion index is roughly equal to 63 + 4 x Z (p < .001), where Z is 1.5 for patients aged 15-19 years, 2.0 for patients aged 20-29 years, 3.0 for patients aged 30-39 years, 4.0 for patients aged 40-49 years, 5.0 for patients aged 50-59 years, and 6.0 for patients aged 60-79 years. CONCLUSION: There is a linear association of marrow conversion index and age. The estimating equation may provide baseline information for the marrow conversion index.

Adolescent↗

Nucleic acid vaccines against hepatitis viruses.

Direct DNA intramuscular or intradermal injection of plasmids containing viral genes under the control of viral promoters is an efficient means of stimulating both class I and class II-mediated antiviral responses. Viral hepatitis B and C are suitable candidates for this approach, particularly as therapeutic immunogens for chronically infected individuals. Several groups have shown that the S gene of HBV is expressed in murine muscle and stimulates a high titre and long-lasting anti-HBs response. Uniquely, CD8+ CTL responses are also induced to HBsAg. No vaccine exists for HCV. Therefore the structural genes (C + E1 + E2) have been cloned as a 2,831 bp fragment from a genotype la isolate into the vector pcDNA3. The resulting plasmid DNA was injected directly into the quadriceps muscle of three-week-old BALB/c mice. Intracellular-expressed E1 and E2 proteins thus represent the complete spectrum of native structural epitopes, including those dependent on glycosylation and protein folding. Mouse antisera were tested for reactivity against conserved sequences using overlapping 7-mer peptides. Two conserved, overlapping epitopes were identified in E2 spanning residues 581-591 and 590-603. This domain represents one of seven major E2 antigenic domains recognized by HCV human antibodies, one of three with antigenic homologies to related flavivirus proteins. Thus antigen is presented with high efficiency following DNA injection and offers the potential of high rates of seroconversion and virus clearance in those predisposed to virus-induced chronic liver disease.

Animals↗

Hepatitis C-related chronic liver disease among asymptomatic blood donors in the north west of England.

In the first 19 months of screening, the North Western Regional Transfusion Centre (RTC) tested 224,000 consecutive blood donors for antibody to hepatitis C virus (anti-HCV) by second generation enzyme immunoassay (EIA). Of these, 366 repeatedly reactive samples were referred for confirmatory testing at Manchester Public Health Laboratory (PHL). There, the initial EIA was repeated, together with two further EIAs. All the referred samples were subjected to a confirmatory line immunoblot (RIBA-II). Reverse transcription followed by the polymerase chain reaction (RT-PCR), in order to detect viral RNA, was performed on selected samples. Among the donors, 61 accepted offers for medical review and were assessed for risk factors, clinical findings and results of standard liver function tests. Of these donors, 53 proceeded to liver biopsy. The overall prevalence of confirmed positive donors was 0.04%. Main risk factors identified included intravenous drug abuse in 31 (51%) donors and prior blood transfusion in 12 (20%) but a risk factor was not apparent in 11 (18%). Viraemia, detected by RT-PCR, could be predicted with a high degree of accuracy by means of the readily available and simpler screening and confirmatory tests (EIA and RIBA-II). Established chronic hepatitis was demonstrated in 90% of the liver biopsies. A trend towards worsening histological findings accompanied increasing concentrations of serum transaminase. Even so, many donors with normal transaminase values had abnormal biopsies including those showing chronic active hepatitis (CAH). These findings indicate that a substantial proportion of previously unrecognised asymptomatic persons with established chronic liver disease exists among North Western blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cognitive, behavioral, and family factors in the differentiation of depressive and anxiety disorders during childhood.

Contribution of cognitive, behavioral, and family environment variables to the differentiation of depressive and anxiety disorders in children was explored. Fifty-nine children from Grades 4-7 (14 diagnosed with a depressive disorder, 16 diagnosed with depressive and anxiety disorders, 11 diagnosed with an anxiety disorder, and 18 nondisturbed controls) completed measures of the depressive cognitive triad, depressive cognitions, social skills, family environment, and maladaptive family messages. Results of a stepwise discriminant function analysis indicated that 2 discriminant functions composed of 7 variables from the cognitive, behavioral, and family environment domains accounted for 91% of the between-groups variance. Results suggest that depressive disorders can be distinguished from anxiety disorders on the basis of ratings of cognition, social skills, and family environment. Implications for existing research and a model of depression during childhood are discussed.

Adolescent↗

Self-reported anger in black high school adolescents.

The purpose of this study was to explore the recognition and expression of anger in black high school adolescents. A total of 56 teens, aged 14-19 years, responded to questions about their recognition of anger, how and to whom they express anger, and to whom they refrain from expressing anger. They also stated their opinions about acceptable and unacceptable expressions of anger and its relationship to depression or suicide. Data were analyzed using frequency tabulations for all questions on the survey instrument. Specific variables of age, grade in school, gender, and family composition were analyzed by one-sample chi 2 tests (alpha set at 0.05). The study demonstrated 1) all the teens surveyed could recognize when they were angry; 2) most teens expressed anger to their friends, to their siblings, and to their mothers; 3) younger teens (ages 14-15 years) when compared to older teens (ages 18-19 years), identified mother as the one who made them angry; 4) females were more likely to feel like crying when angry; 5) females were more likely to feel like being silent when angry; 6) students from one- and two-parent homes did not differ in their expression of anger. Implications of this study include the recognition that anger is a natural, human emotion. Adolescents need to observe adults who can effectively manage behavior associated with anger. Problem solving skills, stress management techniques, and role play situations can be utilized as effective tools in the recognition and expression of anger in acceptable ways and in attempts at the prevention of dysfunctional anger.

Adolescent↗

Acridine araphanes: a new class of probe molecules for biological systems.

The bis-acridine ring system forms the basis for new biophysical probes of novel stereochemistry. Spectral data indicate that certain alkylene bridged bis-9-aminoacridines have a parallel plane conformation of predictable interplane distance. The parallel plane conformation is independent of solvent and thus is different from nucleic acid systems. This stable conformation allows these compounds to be used as sensitive "rulers" for describing binding site geometry in cholinergic enzymes and in the delineation of the mechanism of allosteric control in acetylcholinesterase.

Acetylcholinesterase↗

Megavitamins for minimal brain dysfunction. A placebo-controlled study.

Preliminary to a stimulant comparison study, 31 children with minimal brain dysfunction randomly received either placebo or a megavitamin combination. During a two-week trial, only two children responded so well that stiumlants were not considered necessary; both were in the placebo group. Change scores from pretest to posttest on four blind ratings by teachers and parents did not show a significant difference between the placebo and vitamin groups.

Ascorbic Acid↗

Methylphenidate vs dextroamphetamine vs caffeine in minimal brain dysfunction: controlled comparison by placebo washout design with Bayes' analysis.

Double-blind crossover comparison of methylphenidate hydrochloride, dextroamphetamine sulfate, and caffeine after placebo washout in 29 children with minimal brain dysfunction (MBD) showed on six ratings that methylphenidate and dextroamphetamine were significantly (P less than .05 to P less than .001) better than placebo and caffeine, but not significantly (P less than .05) different from each other. Placebo, caffeine, and ratings before drug did not differ significantly. Of 26 drug responders, 12 responded best to dextroamphetamine, ten to methylphenidate, and one to caffeine. The latter child showed no improvement at all with either prescription stimulant. Methylphenidate and dextroamphetamine were each efficacious for six children who did not respond to the other stimulant. All three drugs showed significant (P less than .05) weight loss and cardiovascular side effects, the latter possibly spurious. Dextroamphetamine showed a significant (P less than .05) decrease from placebo in "tummyaches."

Attention Deficit Disorder with Hyperactivity↗

Effect of milk and casein on the absorption of supplemental iron in the mouse and chick.

Milk is an attractive vehicle for introducing iron supplements into iron-deficient infants and children. This study compares the effects of milk and caseins on the whole-body absorption of radioactive iron complexes in an attempt to resolve the controversy over whether milk and its constituent phosphoproteins seriously impair iron absorption. Evidence is presented to clarify the role of the calcium-casein micelles of cow's milk in binding iron donated by the ferric-nitrilotriacetate (NTA) complex. The absorption of iron from isolated Fe(III)-casein complexes was studied in mice as a function of the casein--to--Fe ratio and was compared with the absorption of Fe(III)-NTA at equivalent levels. Even at casein--to--Fe ratios higher than those found in conventional iron-supplemented cow's milk (10-15 mg Fe/qt; casein P:Fe congruent to 34), absorption of iron(III) from the casein or NTA complex was not significantly different. There was no significant difference in the absorption of iron administered to mice and chicks as ferrous ion, ferric-NTA, or ferric fructose; nonfat cow's milk did not inhibit the absorption of these iron compounds. For the chick, in fact, milk significantly enhanced the absorption of iron from the ferric-NTA chelate. In order to affect iron absorption significantly casein would have to be present considerably in excess of that found in conventionally supplemented cow's milk.

Absorption↗