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Biomedical subjects

J Walker

Publications and source records attributed to J Walker.

At least 19 recordsLinked to original sources

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

An audit of ultrasound diagnosis of gallbladder calculi.

Many series suggest that ultrasound is an accurate method for demonstrating cholelithiasis. However, these series were often prospective and the examinations performed by experienced sonographers. This audit addresses whether the accuracy is maintained in daily practice. We reviewed the ultrasound scans of 128 patients who underwent cholecystectomy for cholelithiasis and compared the findings. The operative and ultrasound findings were at variance in eight of the 128 patients (6.2%). Five were reported as having gallstones on ultrasound but none were found at cholecystectomy, a false positive rate for ultrasound of 3.9%. Three had abnormal gallbladders with no gallstones on ultrasound but gallstones were found at operation, a false negative rate of 2.3%. To avoid false positive diagnoses, suboptimal examinations should be repeated and the scan should be repeated immediately pre-operatively if only small calculi are seen. Alternative imaging should be performed if necessary, either cholescintigraphy in the acute situation or elective oral cholecystography. Some false negative examinations may be avoided by performing repeat examinations if the gallbladder is thick-walled and tender. With these provisos we conclude that ultrasound correctly diagnoses cholelithiasis in daily practice.

Cholecystectomy

Potentiating effects of cigarette smoking and moderate exercise on the thermic effect of a meal.

The purposes of this study were: (i) to determine the relative thermic effects of smoking and exercise in fasted and postprandial states, and (ii) to determine whether there is a weight-controlling caloric advantage of moderate exercise in the postprandial state which might be used upon smoking cessation. The subjects were ten physically fit, young, male smokers. Twenty minutes of smoking (two cigarettes) while fasted resulted in a 6.0% (12.5 kcals/3h) increase in resting metabolic rate (RMR), and 20 minutes of walking (5.8 km/h) while fasted increased post-exercise RMR by 5.8% (11.7 kcals/3h). The thermic effect of a meal (TEM) (740 ml, 874 kcals) increased RMR 21.0% (42.3 kcals/3h), which was increased to 22.1% by smoking (45.0 kcals/3h). Exercise after a meal increased RMR 29.1% (58.1 kcals/3h). Post-prandial exercise potentiated the TEM, as the energy cost was 4.0 kcals/3h greater than the sum of the thermic effect of the meal plus the thermic effect of exercise in the fasted state. Postprandial exercise expended 112.2 kcals/20 min vs. 101.6 kcals/20 min for fasted exercise, a difference of 10.4%. The difference increased to 14.6% when the post-exercise thermic effect was included. It was concluded that the thermic effect of smoking and exercise were similar in the fasted state, but were substantially different postprandially. Moderate postprandial exercise appears to offer a substantial weight-controlling advantage when compared with fasted exercise.

Adult

When self-help begins at home. Pain control in cancer care.

Ineffective pain control prevents many people with advanced cancer from being cared for at home as they would wish. Teaching patients about their analgesia and encouraging the use of complementary techniques can help prevent unnecessary suffering.

Humans