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Biomedical subjects

C Thornton

Publications and source records attributed to C Thornton.

At least 73 records · Page 4Linked to original sources

Wolcott-Rallison syndrome associated with congenital malformations and a mosaic deletion 15q 11-12.

Wolcott-Rallison syndrome is a rare autosomal recessive condition first described in 1972. It is characterised by diabetes mellitus which arises in early infancy and multiple epiphyseal dysplasia. We describe an affected girl who had recurrent episodes of hepatic failure for which no obvious cause was found. Post-mortem examination revealed abnormal pancreatic histology and congenital abnormalities of the central nervous and cardio-respiratory systems which have not been previously described in this condition. She also demonstrated a deletion at 15q 11-12 in 65% of her cells.

Abnormalities, Multiple↗

Orally administered microencapsulated Bordetella pertussis fimbriae protect mice from B. pertussis respiratory infection.

Fimbriae from Bordetella pertussis have been encapsulated in poly(lactide-co-glycolide) microparticles of a size appropriate for uptake by the immune inductive tissues of the gastrointestinal tract. Mice were immunized by oral gavage with a single dose of 10 micrograms of microencapsulated fimbriae. The resulting immune responses were compared with those resulting from intraperitoneal injection of mice with equivalent amounts of fimbriae absorbed onto alhydrogel. The examination of serum and mucosal secretions, collected over a 6-week period, for specific antifimbrial antibodies clearly demonstrated that only orally immunized animals mounted measurable immune responses in external secretions. Six weeks after immunization, all immunized animals were protected against intranasal challenge with live B. pertussis.

Administration, Oral↗

Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines for primary immunisation.

A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to assess antibody response. Data were compared with those from historical controls who had received DTP and PRP-T vaccines by separate injection. The combined vaccine was well tolerated. Rates of local and general reactions were similar to those reported for infants immunised by separate injection. All infants achieved protective antibody titres (> 0.01 IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15 microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3) showed appreciable rise following immunisation. DTP and PRP-T vaccines provide similar antibody responses and adverse effects whether mixed in the same syringe or administered by separate injection. The vaccines could be combined for use in the United Kingdom primary immunisation schedule.

Antibody Formation↗

Polyadenylated RNA, actin mRNA, and myosin heavy chain mRNA in young and old human skeletal muscle.

The myofibrillar protein synthesis rate in old human skeletal muscle is slower than that in young adult muscle. To examine whether this difference in protein synthesis rate is explained by reduced availability of the mRNAs that encode the most abundant myofibrillar proteins, we determined relative hybridization signals from probes for actin mRNA, myosin heavy chain mRNA, and total polyadenylated RNA in vastus lateralis muscle biopsies taken from young (22- to 31-yr-old) and old (61- to 74-yr-old) human subjects. The mean fractional rate of myofibrillar synthesis was 38% slower in the older muscles, as determined by incorporation of a stable isotope tracer. Total actin and myosin heavy chain mRNAs, and polyadenylated RNA, were determined using slot-blot assays. Isoform-specific determinations of alpha-actin mRNA, type I myosin heavy chain mRNA, and type IIa myosin heavy chain mRNA were done with ribonuclease protection assays. Hybridization signals were expressed relative to tissue DNA content. There was no difference between age groups in total polyadenylated RNA or in any of the specific mRNAs. We conclude that the slower myofibrillar synthesis rate in older muscle is not caused by reduced mRNA availability.

Actins↗

Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old.

The rate of synthesis of myofibrillar proteins is slower in muscle of healthy subjects over 60 yr old than it is in young adults. Previous research suggests that reduced activity of the GH/insulin-like growth factor-I system could be a determinant of this slowing of protein synthesis. To test the hypothesis that GH could rejuvenate the rate of myofibrillar protein synthesis, we studied healthy subjects over 60 yr old, after a single injection (0.03 mg/kg.sc) of recombinant human GH (n = 6 males/2 females) or placebo (n = 6 males/2 females), or after 3 months of either GH (0.03 mg/kg, sc, 3 x /week, n = 5 males) or placebo (n = 5 males) treatment. Myofibrillar protein synthesis and whole-body protein metabolism were evaluated with the tracer L-[1-13C]leucine. GH reduced whole-body leucine oxidation by 36% (P < 0.01) in the single injection study. There was no effect of GH on whole-body protein breakdown or synthesis, or on myofibrillar protein synthesis in the quadriceps, either acutely or after 3 months of treatment. GH treatment for 3 months increased lean body mass (3.3 +/- 0.7 kg, P < 0.01, as evaluated by 40K counting), muscle mass (3.3 +/- 1.1 kg, P < 0.02, as evaluated by urinary creatinine excretion), and thigh strength (14 +/- 5%, P < 0.05, as evaluated by isokinetic dynamometry). We conclude that GH can increase muscle mass and strength in healthy men over 60 yr old, but does not restore a youthful rate of myofibrillar protein synthesis.

Aged↗

Preventing diabetic foot disease: lessons from the Medicare therapeutic shoe demonstration.

OBJECTIVES: Every year about 38,000 elderly people with diabetes have a lower extremity amputation. Therapeutic shoes are prescribed by clinicians specializing in foot care to prevent foot ulcerations and amputations among at-risk patients with diabetes. Medicare ran a 3-year demonstration of a therapeutic-shoe benefit for beneficiaries with diabetes. Medicare added the benefit nationwide in May 1993. METHODS: This paper describes the benefit and its implementation in the demonstration based on demonstration records, a patient survey, and discussions with clinicians and shoe suppliers before and during the demonstration. RESULTS: During the demonstration, far fewer beneficiaries applied for the therapeutic shoes than were eligible for them. The paper discusses reasons for the low beneficiary application rate and the associated low participation rate among physicians treating patients with diabetes. CONCLUSIONS: The benefit is unlikely to be used any more in the national program than in the demonstration unless physicians are educated in the role therapeutic shoes can play in diabetic foot disease, they prescribe the shoes for their patients, and they increase their patients' awareness of the shoes' value.

Centers for Medicare and Medicaid Services, U.S.↗

Constitutive expression of major histocompatibility complex class II antigens on monocytes and B cells correlates with disease in simian immunodeficiency virus-infected rhesus macaques.

Constitutive host factors that influence progression to AIDS are understood poorly. In the macaque model for AIDS, 35 animals infected with simian immunodeficiency virus (SIV) were analyzed for major histocompatibility complex class II antigen expression on blood monocytes and B cells by immunostaining and flow cytometry. Expression varied widely between animals but was constant with time. Level of expression and the proportion of monocytes and B cells that expressed class II were not affected by SIV infection. Significantly more animals developed AIDS in the group with low class II expression than in the group with high expression (P < .001). Progression to disease was faster in animals that expressed poorly (P < .01), and opportunistic pathogens were more common (P < .05). Thus, the constitutive level of class II antigen expression may be a useful prognostic indicator for human immunodeficiency virus disease in humans and may be an important factor in the design of vaccine trials.

AIDS Vaccines↗

Myofibrillar protein synthesis in young and old human subjects after three months of resistance training.

Muscle protein synthesis is slower in healthy older men and women than in young adults, but whether this results from relative disuse rather than aging is unclear. The present study was done to examine rates of myofibrillar protein synthesis before and after a 3-mo progressive resistance exercise program in young and old men and women. Protein synthesis was determined by incorporation of the tracer L-[1-13C]leucine into myofibrillar proteins obtained from the vastus lateralis muscle by needle biopsy. Before exercise, mean fractional myofibrillar synthesis was 33% slower (P < 0.01) in nine older subjects (62-72 yr old, 5 men and 4 women) than in 9 young subjects (22-31 yr old, 5 men and 4 women). Initial strength, as determined by three-repetition-maximum tests, was significantly less in the older group. Strength and training weights increased similarly in young and old groups, when expressed in relation to baseline values. Posttraining myofibrillar synthesis was determined on the day after the final training session. There was not a significant change in fractional myofibrillar synthesis in either the young or the old group after training, and the rate in the older group remained 27% slower (P < 0.05). Whole body protein turnover increased approximately 10% only in the younger group, and 24-h urinary 3-methylhistidine excretion (an index of myofibrillar proteolysis) was not significantly affected by training. These data suggest that the slower myofibrillar synthesis rate in older subjects cannot be explained by disuse.

Adult↗

Postprandial myofibrillar and whole body protein synthesis in young and old human subjects.

Rates of incorporation of leucine (using L-[1-13C]leucine as a tracer) into myofibrillar and whole body proteins were determined in healthy old (> 60 yr old, n = 7) and young (< 30 yr old, n = 9) men and women who were fed small meals (4% of daily energy) every 30 min. There was no difference in whole body incorporation of leucine into proteins in the young (148 +/- 5 mumol.h-1.kg lean body mass-1, means +/- SE) and old groups (150 +/- 3 mumol.h-1.kg lean body mass-1). However, the fractional myofibrillar protein synthesis in the vastus lateralis muscle was 28% slower in the older group (0.063 +/- 0.004 vs. 0.088 +/- 0.003 %/h, P < 0.001). Extrapolation of these results to whole body myofibrillar synthesis (fractional rate x myofibrillar mass estimated by creatinine excretion) indicated that, in the older group, total myofibrillar synthesis was 43% slower (1.8 +/- 0.2 vs. 3.1 +/- 0.2 g/h, P < 0.01) and that their myofibrillar synthesis was a smaller portion of whole body protein synthesis (15 +/- 1 vs. 23 +/- 1%, P < 0.001). Compared with age-matched postabsorptive subjects, whole body protein synthesis was approximately 25% faster, and fractional myofibrillar synthesis was approximately 50% faster in these fed subjects, both young and old. We conclude that myofibrillar synthesis is slower in older subjects during both postabsorptive and postprandial conditions but that aging does not impair the stimulatory effect of feeding on protein synthesis.

Adult↗

A study of the relation between eating disorder and death concern.

The relationship between eating disorder and various components of death orientation (fear, anxiety, acceptance and concern) was examined, taking into account the level of depression in patient samples as well as elements of religiosity. The results were not able to support more than a very modest relationship between eating disorder and death orientation. Eating disorder patients could not be distinguished from other clinical controls, nor did anorexia nervosa patients differ from other eating disorder patients in this respect. Beck and Beck [20] depression scores were higher in the non eating disordered clinical sample than in the eating disorder group, and death concern was shown to be related to the severity of depression. Religiosity did not appear important when indices of religiosity were considered, but did emerge as an important factor in the "free information" provided by participants.

Adolescent↗

Dreams of death: Von Weizsäcker's Dreams in so-called endogenic anorexia: a research note.

Viktor Von Weizsäcker's paper "Dreams in so-called endogenic Magersucht (anorexia," first published in the Deutsche Medizinische Wochenschrift in 1937 (translation in M. Kaufman & M. Heiman [1964]. Evolution of psychosomatic concepts: Anorexia nervosa: A paradigm (pp. 181-197), New York: International Universities Press, has been described as a noteworthy and historically important contribution to the recognition of anorexia nervosa as a psychosomatic illness. Von Weizsäcker analyzed the dreams of patients he was treating for "endogenous anorexia" (magersucht). He claimed that in the bulimic phase his patients experienced nightmares dealing with themes of death, but that in the anorectic phases of restricted eating more pleasant dreams dealt with themes of blissful contentment. The authors draw current attention to his work as another early example of the treatment of the theme of death and death symbolism in the literature on eating disorders, and suggest some reappraisal of von Weizsäcker's interpretations of his own material.

Anorexia Nervosa↗

Myofibrillar protein synthesis in young and old men.

We tested the hypothesis that healthy older men (> 60 yr old) have a slower rate of myofibrillar protein synthesis than young men (< 35 yr old). Myofibrillar protein synthesis was determined by the in vivo incorporation of L-[1-13C]leucine into myofibrillar proteins obtained by muscle biopsy. Subjects were eight young (21-31 yr) and eight older (62-81 yr) men, all healthy and moderately active. There was no significant difference in the mean height and weight of the two age groups, but the older group had 12% less lean body mass (determined by 40K counting) and 21% less muscle mass (estimated by urinary creatinine excretion). Upper leg strength was approximately one-third lower in the older subjects according to isokinetic dynamometry. The fractional rate of myofibrillar protein synthesis was 28% slower in the older group (0.039 +/- 0.009 vs. 0.054 +/- 0.010 %/h, mean +/- SD, P < 0.01). Total myofibrillar protein synthesis, estimated as total myofibrillar mass (from creatinine excretion) times the fractional synthesis rate, was 44% slower in the older group (1.4 vs. 2.5 g/h, P < 0.001). Whole body protein synthesis, assessed as the difference between leucine disappearance rate and leucine oxidation, was marginally slower (8%, P = 0.10) in the older group, but not when the data were adjusted for lean body mass. Myofibrillar protein synthesis was a smaller fraction of whole body protein synthesis in the older group (12 vs. 19%). Reduced myofibrillar protein synthesis may be an important mechanism of the muscle atrophy associated with aging.

Adult↗