The distribution of cathepsin B in human tissues

Cathepsin B is a lysosomal enzyme of importance in many physiological and pathological processes. Its distribution in human tissues was studied by an indirect immunoperoxidase method. Cathepsin B was demonstrated in macrophages, hepatocytes, renal tubules, gastrointestinal epithelium and fibroblasts, confirming previous studies. It was demonstrated for the first time by immunohistology in several other tissues, especially stratified squamous epithelium, transitional epithelium, salivary glands, pancreas, central and peripheral neuronal cell bodies, trophoblast and all endocrine organs. Widespread distribution of cathepsin B has been postulated several times but this is the fullest evidence that the enzyme indeed occurs in many organs. In pathology cathepsin B has so far been thought to be involved in demyelination, emphysema, rheumatoid arthritis and neoplastic infiltration.     

Interaction of nutrition and infection: effect of copper deficiency on resistance to Trypanosoma lewisi.

The copper-deficient rat-trypanosome system was used to study copper deficiency in Sprague Dawley rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lower plasma and liver copper concentrations compared with complete and pair-fed animals. In all dietary groups, the food intake and body weight changes of rats inoculated with T lewisi showed significant increases over the noninoculated controls. The rate of these indices were significantly less in the copper-deficient animals compared with the animals fed complete diets. Copper-deficient and pair-fed control rats showed greater numbers of parasites than controls throughout the infection. The duration of the trypanosomal infection was longer in copper-deficient rats compared with other groups. In all of the dietary groups, severe depression in the primary and secondary antibody responses (IgM and IgG) to in vivo immunization with sheep erythrocytes was observed in infected animals over noninfected controls. The results of the present study indicate that during copper deficiency, there are significant changes in food consumption and body weight and enhanced susceptibility to infection as measured by an increased parasitemia and depression in the antibody responses.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Clostridium difficile: clinical disease and diagnosis.

Clostridium difficile is an opportunistic pathogen that causes a spectrum of disease ranging from antibiotic-associated diarrhea to pseudomembranous colitis. Although the disease was first described in 1893, the etiologic agent was not isolated and identified until 1978. Since clinical and pathological features of C. difficile-associated disease are not easily distinguished from those of other gastrointestinal diseases, including ulcerative colitis, chronic inflammatory bowel disease, and Crohn's disease, diagnostic methods have relied on either isolation and identification of the microorganism or direct detection of bacterial antigens or toxins in stool specimens. The current review focuses on the sensitivity, specificity, and practical use of several diagnostic tests, including methods for culture of the etiologic agent, cellular cytotoxicity assays, latex agglutination tests, enzyme immunoassay systems, counterimmunoelectrophoresis, fluorescent-antibody assays, and polymerase chain reactions.     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

Neuropsychological functioning in end-stage renal disease.

AIMS: To compare the neuropsychological functioning and behaviour of children with non-syndromic end-stage renal disease (ESRD) and sibling controls. METHODS: The study was carried out at two tertiary care paediatric teaching hospitals, in Halifax and Vancouver, Canada. Children with ESRD were on a renal transplant waiting list and either pending dialysis or on dialysis therapy. Twenty two patient-sibling pairs were evaluated. Neuropsychological assessments consisting of measures of intelligence, academic achievement, memory, and motor abilities were carried out. Maternal ratings of behaviour and self-report rating of self-esteem were collected. RESULTS: The Verbal, Performance, and Full Scale IQs of patients with ESRD were significantly lower than the IQs of the sibling controls. The mean differences were 8.6, 11.7, and 10.9 points, respectively. ESRD patients also had significantly more difficulty on measures of fine motor coordination and ability to copy geometric designs than sibling controls. There were no differences between groups on measures of academic achievement, memory, behaviour, or self-esteem. CONCLUSIONS: Although children with ESRD exhibited mild deficits on measures of intelligence and some measures of motor abilities, their neuropsychological outcome was more favourable than earlier reports indicated.     

Review: Modelling placental amino acid transfer − From transporters to placental function

Amino acid transfer to the fetus is dependent on several different factors. While these factors can be understood in isolation, it is still not possible to predict the function of the system as a whole. In order to do this an integrated approach is required which incorporates the interactions between the different determinants of amino acid transfer. Computational modelling of amino acid transfer in the term human placenta provides a mechanism by which this integrated approach can be delivered. Such a model would be invaluable for understanding amino acid transfer in both normal and pathological pregnancies.In order to develop a computational model it is necessary to determine all the biological factors which are important contributors to net amino acid transfer and the ways in which they interact. For instance, how different classes of amino acid transporter must interact to transfer amino acids across the placenta. Mathematically, the kinetics of each type of transporter can be represented by separate equations that describe their transfer rate as a non-linear function of amino acid concentrations. These equations can then be combined in the model to predict the overall system behaviour. Testing these predictions experimentally will demonstrate the strengths and weaknesses of the model, which can then be refined with increasing complexity and retested in an iterative fashion.In this way we hope to develop a functional computational model which will allow exploration of the factors that determine amino acid transfer across the placenta. This model may also allow the development of strategies to optimise placental transfer in pathologies associated with impaired amino acid transfer such as fetal growth restriction.     

Children's health care: Book and media reviews

Let's Remember Corky, Fine, Polly Delson, Shaker Heights, Ohio, 1981. Paperback, unpaged, $4.75.

The Tenth Good Thing about Barney, Viorst, Judith, Hartford, Atheneum, 1971. Paperback, 20 pages, illustrated by Erik Blegvad.

Jasper Enters the Hospital, 16½ mins., The Day of Jasper's Operation, 13½ mins., Wellness: It's Not Magic, 15 mins., Video Cassettes‐ 16 mm. Available from: Kids Corner, 2027 North Tejon Street, Colorado Springs, Colorado 80907, (303) 475–2499.

First Do No Harm, produced by Pierce Atkins Corporation, 45 mins., S400 (purchase), S45 (daily rental). Distributed by Children's Hospital National Medical Center, 111 Michigan Avenue, N.W., Washington, D.C. 20010.

Pediatric Diagnostic Procedures With Guidelines for Preparing Children for Clinical Tests, Droske, Susan C. and Francis, Sally A. Toronto, John Wiley and Sons Inc., 1981.

The Children's Medical Series ‐ a series of eight videotapes with Susan Linn and her puppets.     

Patient perspectives on the physical,psycho-social,and financial impacts of diabetic foot ulceration and amputation

AimsDiabetic foot ulcers (DFUs) and ulceration are complex and lifelong problems for patients with diabetes which dramatically increase mortality rates. This qualitative study sought to capture detailed personal accounts and insights from patients with a clinical history of DFUs and amputations to better understand patient experiences.MethodsFifteen patients from a tertiary referral center that treats diabetic foot problems were approached for participation. Inclusion criteria included having at least one DFU and being of white, Native American, or Hispanic background. Interviews were conducted by telephone by study staff trained in qualitative data gathering and audio recorded.ResultsThe main themes that emerged around impacts included the heavy burden of managing care, significant loss of ambulatory function, economic stress due to medical care costs and job loss, and emotional suffering tied to these stressors.ConclusionsThese data illuminate common social and personal impacts of diabetic foot problems across an ethnically and racially diverse and predominantly low-income US sample that expand our understanding of related declines in well-being. Our results indicate a need for proactive mental health assessment post DFUs diagnosis and the diversification of hospital and community-based support systems.