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Biomedical subjects

J Walker

Publications and source records attributed to J Walker.

At least 271 records · Page 15Linked to original sources

Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group.

OBJECTIVE: To compare the effects of placebo and GLA on the course of mild diabetic neuropathy over 1 yr. RESEARCH DESIGN AND METHODS: We entered 111 patients with mild diabetic neuropathy from seven centers into a randomized, double-blind, placebo-controlled parallel study of GLA at a dose of 480 mg/day. MNCV, SNAP, CMAP, hot and cold thresholds, sensation, tendon reflexes, and muscle strength were assessed by standard tests in upper and lower limbs. RESULTS: For all 16 parameters, the change over 1 yr in response to GLA was more favorable than the change with placebo, and for 13 parameters, the difference was statistically significant. Sex, age, and type of diabetes did not influence the result, but treatment was more effective in relatively well-controlled than in poorly-controlled diabetic patients. CONCLUSIONS: GLA had a beneficial effect on the course of diabetic neuropathy.

Analysis of Variance↗

Cardiac risk factors immediately following spinal injury.

Cardiac risk factors were evaluated in 48 persons (39 males, 9 females) with quadriplegia or paraplegia, resident in a specialized spinal injury hospital and seen 0.3 +/- 0.7 years after their spinal injury. The majority of the patients reported being extremely active physically prior to injury. Limited activity in the hospital involved the use of ergometers, pulleys, and weights; however, the majority of subjects expressed a wish for more exercise. Serum lipid profiles showed a relatively normal total cholesterol (mean 4.58 +/- 0.77 mmol/L), a very low high-density lipoprotein-cholesterol (0.91 +/- 0.27 mmol/L), a relatively normal low-density lipoprotein-cholesterol (2.86 +/- 0.68 mmol/L) and high triglycerides (1.89 +/- 0.88 mmol/L). Resting blood pressures were normal. The percentage of smokers (25%) was similar to the percentage of smokers in the general population, but many had quit smoking subsequent to hospitalization. Family histories and diet gave no evidence of increased cardiac risk. We conclude that individuals who sustain a spinal injury do not have a large inherent risk of cardiac events. In persons with paraplegia, cardiac problems develop mainly from the cumulative impact of reduced physical activity and a resulting adverse lipid profile. There may also be a reactive deterioration in other aspects of personal lifestyle, such as cigarette smoking after leaving the hospital. In high-level lesions, factors such as hypertension and a poor stroke volume with compensatory tachycardia may increase cardiac work rate during attempts at ambulation, further predisposing an individual to myocardial ischemia and cardiac arrest.

Adult↗

Increasing calcium intake in women on a low-fat diet.

Dietary advice to reduce the risk of coronary heart disease (CHD) is aimed at reducing saturated fat intake, especially in people with hyperlipidaemia. Dairy products contribute a considerable proportion of the fat intake of many people's diet in New Zealand, and are thus often reduced. However, dairy products provide about 60% of the dietary calcium. This study investigated the calcium intake of 50 women aged 40-65 years on fat-reduced diets. The effect of giving standardized information on the importance of calcium intake, and on ways to increase this, was assessed by a repeat dietary analysis 3 months later. The mean (SD) calcium intake was initially 696 (245) mg per day; below that recommended for post-menopausal women. The mean percentage energy from fat and saturated fat was 28.5% and 9.6%, respectively. Three months later, after the specific advice on calcium, the mean calcium intake was significantly higher at 938 (317) mg per day, with 88% having increased their intake, yet the intake of energy, fat and saturated fat were unchanged. This was mainly achieved by increased use of low-fat dairy products. Specific advice about calcium should be given to women commencing lipid-lowering diets in order to attain recommended intakes and to reduce the risk of osteoporosis, as well as CHD.

Adult↗

Effect of deferoxamine on retinal lipid peroxidation in experimental uveitis.

PURPOSE: To examine the effect of deferoxamine, an effective iron chelator, on experimental autoimmune uveitis. Because deferoxamine has been shown to reduce iron-catalyzed hydroxyl radical generation, the in vivo effect was sought in the experimental autoimmune uveitis-mediated retinal lipid peroxidation, which is presumably induced by the inflammatory cell-derived oxygen radicals including hydroxyl radicals. METHODS: The experimental uveitis was induced in Lewis rats by retinal S-antigen. Deferoxamine infusion by osmotic pumps was started 2 days before the onset of the disease and was continued for 7 days. The extent of retinal lipid peroxidation was measured by the production of conjugated dienes, ketodienes, and thiobarbituric acid active substances. The inflammation associated free radical activity was measured by the luminol-amplified chemiluminescence. RESULTS: Levels of conjugated dienes, ketodienes, and thiobarbituric acid reactive substances were significantly decreased in the deferoxamine-treated animals. With Student's t test, the P values are < 0.025 for conjugated dienes between deferoxamine- and sham-treated animals; < 0.025 for ketodienes between deferoxamine- and sham-treated animals; and < 0.01 for thiobarbituric acid reactive substances between deferoxamine- and sham-treated animals. With in vitro addition of 10 mM deferoxamine, the free radical generation of inflamed retina was suppressed by nearly 40%. CONCLUSIONS: The administration of deferoxamine resulted in reduction of retinal lipid peroxidation. Because photoreceptors contain a high proportion of polyunsaturated fatty acids, deferoxamine, in turn, will act to ameliorate the experimental autoimmune uveitis-mediated retinal degeneration.

Animals↗

Induction of mucosal and systemic immunity to a recombinant simian immunodeficiency viral protein.

Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4+ T cell proliferative and helper functions in the circulating blood.

Administration, Oral↗

A highly conserved repeated DNA element located in the chromosome of Streptococcus pneumoniae.

We report the discovery of a group of highly conserved DNA sequences located, in those cases studied, within intergenic regions of the chromosome of the Gram positive Streptococcus pneumoniae. The S. pneumoniae genome contains about 25 of these elements called BOX. From 5' to 3', BOX elements are composed of three subunits (boxA, boxB, and boxC) which are 59, 45 and 50 nucleotides long, respectively. BOX elements containing one, two and four copies of boxB have been observed; boxB alone was also detected in one instance. These elements are unrelated to the two most thoroughly documented families of repetitive DNA sequences present in the genomes of enterobacteria. BOX sequences have the potential to form stable stem-loop structures and one of these, at least, is transcribed. Most of these elements are located in the immediate vicinity of genes whose product has been implicated at some stage in the process of genetic transformation or in virulence of S. pneumoniae. This location raises the intriguing possibility that BOX sequences are regulatory elements shared by several coordinately controlled genes, including competence-specific and virulence-related genes.

Base Sequence↗

Familial clustering of cardiovascular disease in patients with insulin-dependent diabetes and nephropathy.

BACKGROUND: Patients who have insulin-dependent diabetes mellitus and nephropathy have an excess of cardiovascular disease. Familial factors may in part account for this phenomenon. METHODS: We identified 61 white patients under 65 years of age with insulin-dependent diabetes who had nephropathy, and then matched them with 61 diabetic patients without nephropathy. We determined the prevalence of cardiovascular disease in the parents of these patients with use of information obtained from death certificates or from the World Health Organization questionnaire for cardiovascular disease. RESULTS: The rates of ascertainment of information were 96 percent (n = 117) for the parents of diabetic patients with nephropathy and 95 percent (n = 116) for the parents of patients without nephropathy. Cardiovascular disease was more often a direct cause of death among the parents of diabetic patients with nephropathy (40 percent vs. 22 percent, P less than 0.03), and the combined morbidity and mortality from cardiovascular disease in this group was greater than that in the parents of diabetic patients without nephropathy (31 percent vs. 14 percent, P less than 0.01). The age-adjusted and sex-adjusted relative risk of cardiovascular disease in this group of parents was 2.9 (95 percent confidence interval, 1.5 to 5.5; P less than 0.001). Moreover, a paternal history of cardiovascular disease was associated with a significantly increased risk of nephropathy in the diabetic patient after the analysis was adjusted for age, sex, and duration of diabetes (odds ratio, 3.2; 95 percent confidence interval, 1.3 to 7.9; P less than 0.01). Among the diabetic patients with nephropathy, those who had had a cardiovascular event were much more likely to have a family history of cardiovascular disease (odds ratio, 6.2; 95 percent confidence interval, 2.0 to 19.0; P less than 0.005) than those who had not had such an event. CONCLUSIONS: Among patients with insulin-dependent diabetes, a parental history of cardiovascular disease is significantly associated with the development of nephropathy and, among those with nephropathy, increases the likelihood of cardiovascular disease.

Adolescent↗

Biochemical characterisation of the enzyme responsible for "activated L-serine sulphydrase" activity in nematodes.

The biochemical properties of the enzyme responsible for nematode "activated L-serine sulphydrase" activity (L-cysteine + R-SH----cysteine thioether + H2S) have been investigated using primarily the gastro-intestinal nematodes Nippostrongylus brasiliensis and Haemonchus contortus. The activated L-serine sulphydrase enzyme was found to be cytosolic in origin and exhibited maximal activity at pH 9.0. Enzyme activity was widely distributed amongst the major tissues of adult female Ascaris suum but was particularly abundant in longitudinal muscle. The enzyme appeared to have a rigid specificity for L-cysteine as the primary thiol substrate, but was capable of utilising a number of sulphur amino acids (and derivatives) and nonphysiological thiols as second substrates. The best second thiol substrates were nonphysiological, hydroxyl-containing thiols that showed some structural similarity to the standard second substrate, 2-mercaptoethanol. Kinetic analyses revealed that the enzyme operates by a sequential catalytic mechanism, and the absolute Michaelis constants were: KL-cysteine = 0.21 +/- 0.02 mM and K2-mercaptoethanol = 5.58 +/- 0.59 mM. The enzyme was relatively insensitive to inhibition by a variety of substrate analogues and known inhibitors of pyridoxal 5'-phosphate dependent enzymes, whilst plant phenols caused significant levels of inhibition. The most potent inhibitors discovered were the anthelmintics bithionol, dichlorophene and hexachlorophene. Further characterisation revealed that hexachlorophene was a parabolic competitive inhibitor of the activated L-serine sulphydrase enzyme.

Animals↗

The identification of a variant form of cystathionine beta-synthase in nematodes.

Characterization of the physical and catalytic properties of the enzyme responsible for nematode "activated L-serine sulfhydrase" activity (L-cysteine + R-SH-->cysteine thioether + H2S) has led to its identification as a novel, variant form (allelozyme) of cystathionine beta-synthase that is distinct from a mammalian-type synthase also present in nematodes. Additional work has demonstrated the ability of live Panagrellus redivivus to produce H2[35S] from exogenous L-[35S]cysteine and 2-mercaptoethanol, thus providing preliminary evidence for the in vivo operation of the activated L-serine sulfhydrase reaction in nematodes.

Animals↗

Longitudinal study of Toxoplasma seroprevalence in South Yorkshire.

Serum samples collected from individuals of a wide range of ages in South Yorkshire between 1969 and 1990 provided the basis for a longitudinal seroprevalence survey of Toxoplasma gondii antibodies. Sera numbering 3868 were screened for T. gondii specific antibodies using a commercial latex agglutination test. The resultant temporal series of serological profiles revealed a rise, with age, in seroprevalence, the rate of which showed a decrease through time. A plateau of around 40-50% prevalence was attained by the 41- to 45-year age-class in 1969 which was not approached until the 66- to 70-year class in the 1988-90 data set. This trend for decline in seroprevalence was confirmed by statistical analysis for the age range 21-60 years. These results may be indicative of a decrease in the rate of toxoplasma exposure in this study community over the 20-year period. The survey of 1988-90 provides a base-line profile of present-day seroprevalence in which 11% of individuals in the age range 16-45 years (roughly corresponding to the childbearing age-range) show evidence of past infection. The representative nature of the serum collection and public-health implications of these results are discussed.

Adolescent↗

A model for faculty practice teaching clinics developed at the Oregon Health Sciences University.

In 1988 the Oregon Health Sciences University established its first faculty practice teaching clinic wherein physicians in training were incorporated into a faculty private practice clinic; this pilot project proved very successful and has been subsequently adopted as the model for essentially all outpatient clinics (both medical and surgery) in the university system. The model encourages efficiency, overhead control, and appropriate staffing; it also compensates faculty members for their additional time spent teaching. The authors conclude this model may help other academic training centers adapt to the changing demands of medical education.

Academic Medical Centers↗

The nucleotide sequences of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant.

We have shown previously that, compared to other enteroviruses, the coxsackievirus A9 (CAV-9) prototype strain, Griggs, contains a C-terminal extension to the capsid protein VP1 and that within this extension there is an RGD (arginine-glycine-aspartic acid) motif. To determine whether these features are found in other CAV-9 strains and therefore analyse whether they are likely to be functionally important, we have determined the nucleotide sequence of the appropriate region from five strains, isolated over a 25 year period. The results indicate that there is considerable diversity between the strains and there is little correlation between nucleotide sequence identity and date of isolation. All isolates exhibit the VP1 extension and although its amino acid sequence is otherwise variable, the RGD motif is common to all. This conservation of sequence, within a region which can otherwise vary, implies that the RGD sequence must be functionally significant. The VP1 extension shows similarity to sequences found in foot-and-mouth-disease virus strains and to part of the precursor of the cellular protein, human transforming growth factor beta, and the possible significance of these observations is discussed.

Amino Acid Sequence↗

The growth of low-birth-weight children.

The growth of 171 seven-year-old children, free from major disability, with a birth weight of 2000 g or less was examined and compared with that of their own parents and of normal-birth-weight peers. Measurements included height, weight, occipitofrontal circumference, biparietal, occipitofrontal and bi-iliac diameters, triceps and subscapular skinfold thickness. Low-birth-weight children were shorter than their parents whereas those of normal birth weight were taller. For all parameters, particularly weight, the low-birth-weight children were significantly less well grown. There was no significant relationship between occipitofrontal circumference and intellectual ability.

Anthropometry↗