Immune modulation by cadmium and lead in the acute reporter antigen-popliteal lymph node assay.

Immune modulation by heavy metals may cause serious adverse health effects in humans, although the mechanisms involved are not well understood. Both cadmium and lead are important environmental and occupational toxins. Therefore, in the current study, the costimulatory/adjuvant effects and the T-cell-activating potential of these metals (i.e., CdCl2 and PbCl2), are examined. These immune-modulating properties are critical in the development of conditions such as allergy, hypersensitivity, and autoimmunity. Using the direct popliteal lymph node assay (PLNA) and reporter antigen-popliteal lymph node assay (RA-PLNA) both metals were examined individually for immunotoxicity. Mercury (i.e., HgCl2) was included for comparative purposes as its effects in the RA-PLNA are well documented. Seven days following a single footpad injection containing metal and/or RA (trinitrophenyl-ovalbumin [TNP-OVA] or TNP-Ficoll), BALB/c mice were sacrificed and the popliteal lymph nodes (PLNs) removed. PLN cellularity, TNP-specific antibody-secreting cells (ASCs), and lymphocyte subsets were assessed. All three metals strongly stimulated T- and B-cell proliferation and ASC production following coinjection with the RA TNP-OVA. In each case, ASC production was skewed towards the IgG1 isotype. In addition, all three metals induced IgG production to TNP-Ficoll (although relatively weakly in the case of Cd). These results show that each of these metals can provide adjuvant signals to promote lymphocyte proliferation and enhance adaptive immune responses to unrelated antigens. Skewing of immune responses towards T helper type 2 responses suggests that each of these metals can enhance allergic and hypersensitivity reactions to environmental antigens. Furthermore, the induction of IgG responses to TNP-Ficoll, a T-cell-independent antigen, indicates that each of these metals can activate neoantigen-specific T cells. T-cell activation by metals can lead to metal hypersensitivity and has been implicated in the development of autoimmunity. This is the first report of immune modulation by CdCl2 and PbCl2 in the RA-PLNA.     

Importance of speech production for phonological awareness and word decoding: The case of children with cerebral palsy

The goal of this longitudinal study was to investigate the precursors of early reading development in 52 children with cerebral palsy at kindergarten level in comparison to 65 children without disabilities. Word Decoding was measured to investigate early reading skills, while Phonological Awareness, Phonological Short-term Memory (STM), Speech Perception, Speech Production and Nonverbal Reasoning were considered reading precursors. Children with cerebral palsy lag behind on all reading precursors at the beginning of the second year of kindergarten. For the children without disabilities, early reading skills in Grade 1 were best predicted by Phonological Awareness and Phonological STM while Speech Production was the most important predictor of early reading success for the children with cerebral palsy, followed by Phonological Awareness and Speech Perception. Furthermore, for children with cerebral palsy, Speech Production appears to dominate reading development, as Speech Production measured at the beginning of the second year of kindergarten was strongly predictive of all other reading precursors measured at the end of the second year of kindergarten. The results of this study reveal that children with cerebral palsy with additional speech impairments are at risk for limited literacy development. Clinical implications are discussed.     

Adipose tissue fatty acid composition and its relations to diet and plasma lipid concentrations in hemodialysis patients

Adipose tissue fatty acid composition, serum lipid profile, and dietary intake of 37 patients on maintenance hemodialysis were studied. In August 1982, 1984, and 1986, analyses were carried out in 15 normotriglyceridemic (NTG) and 22 hypertriglyceridemic (HTG; type IV hyperlipidemia) patients. No correlations were found between dietary intake of polyunsaturated fatty acids (PUFAs), ratio of polyunsaturated to saturated fatty acids (P-S ratio), and carbohydrate content on the one hand and serum lipid concentrations on the other in the two groups. Adipose tissue linolenic acid correlated negatively with serum cholesterol in both groups. Strong correlations were found between dietary intake of PUFAs and adipose tissue linoleic acid content, between PUFAs and the double-bond index, between P-S ratio and adipose tissue linoleic acid content, and between P-S ratio and the double-bond index. No significant differences in dietary intake or adipose tissue fatty acid composition were observed between NTG and HTG patients. Thus, no evidence was found for exogenous dietary influences on serum lipid concentrations. The adipose tissue linoleic acid content did reflect the dietary intake of PUFAs.     

Transplantability of human head and neck squamous cell carcinomas in athymic nude mice

Tumor material from 91 patients with squamous cell carcinoma of the head and neck was transplanted subcutaneously in athymic nude mice. In the first (man to mouse) passage, the calculated mean probability of tumor take in a single mouse was 11%. The probability of growth in the first passage was significantly better for moderately and poorly differentiated tumors than for well-differentiated tumors. Also, the implantation of lymph node material resulted in a significantly better tumor take rate than material taken from a primary tumor. Transplantability was not dependent on the following characteristics: localization, T or N stage of the tumor, or the sex of the patients. Once growth was established, all variables studied had no influence on the probability of growth in the subsequent mouse passages. A relationship between tumor growth in nude mice and patient prognosis could not be found. When transplanting head and neck squamous cell carcinoma in nude mice, it has to be recognized that some tumor characteristics will influence the success of tumor growth.     

Arterial and venous effects of serotonin in the forearm of healthy subjects are not age-related

The influence of age on the regional arterial and venous effects of serotonin (5-HT) was investigated in 13 young (aged 22-31 years) and seven older (aged 50-69 years) healthy volunteers. Single-dose infusions of 5-HT (1, 10, and 80 ng/kg/min) and of the 5-HT2 receptor antagonist ritanserin (50, 150, and 500 ng/kg/min) were administered into the brachial artery. Subsequently, the relative arterial and venous effects of the highest dose of 5-HT were investigated. Forearm blood flow (FBF) and maximum venous outflow (MVO) were measured by venous occlusion plethysmography. Heart rate (HR) and intraarterial (i.a.) blood pressure were recorded semicontinuously. In both age groups, 5-HT induced an initial transient arterial dilation, followed by a persistent increase in FBF for the doses of 1 and 10 ng/kg/min and a relative small decrease in FBF for the highest dose. In both age groups, the highest dose of 5-HT induced a similar large reduction in MVO (p less than 0.05 for both). The reduction in MVO was attenuated by ritanserin (500 ng/kg/min, p less than 0.05 for both groups). In the younger subjects, this dose of ritanserin also unmasked an arterial dilator effect of the highest dose of 5-HT (p less than 0.05). The single infusions of ritanserin did not influence FBF significantly in either study group. No significant differences were observed between the age groups. These results show that in the forearm of healthy subjects arterial and venous vascular responses to 5-HT were not age-related. In the arterial vascular bed, 5-HT acted predominantly as a vasodilator; at high doses, mainly venous vasoconstriction was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rhinitis Symptom Utility Index (RSUI) in Chinese Subjects: A Multiattribute Patient-preference Approach

Background: The Rhinitis Symptom Utility Index (RSUI), originally developed in the United States, consists of a patient-preference weighting scheme and a 10-item questionnaire measuring the severity and frequency of rhinitis related symptoms over a 14-day period. This study aimed to determine whether the Chinese RSUI could adopt the US-based multi-attribute utility function (MAUF) in scoring rhinitis symptoms. Methods: In a Hong Kong study, 116 Chinese adults with allergic rhinitis completed the RSUI questionnaire and 36-item Short-Form Health Survey (SF-36) after they had been seen by two otorhinolaryngologists for disease-severity ratings. Respondents then completed computer-administered direct preference measures, i.e., visual analogue scale (VAS) and standard gamble (SG) assessments. The VAS and SG data were used to estimate a MAUF for the Chinese-based RSUI. Results: The derived MAUF was somewhat different than the one developed for the US RSUI. Test–retest reliability for the Chinese RSUI was satisfactory (ICC = 0.71, p<0.001). Scores differentiated among cases with mild, moderate, and severe symptoms (p<0.001); and between those who did and did not require medications to control symptoms (p = 0.031). Findings were significantly correlated with SF-36 domain scores (r = 0.19 to 0.37; p=0.041 to <0.001). When the US-based scoring function was applied to the Chinese subjects, the resulting mean RSUI score was significantly lower (p<0.001). Comparisons between directly measured VAS and SG scores between the US and Chinese samples, demonstrated significant differences (all p<0.05), with the US subjects consistently rating rhinitis symptoms as worse than Chinese subjects. Conclusions: The Chinese RSUI has good measurement properties that reflect patient preferences from the Chinese. Results suggest that there are differences in preference rating between US and Chinese subjects and that use of the US-based preference function for the RSUI would bias the measurement of rhinitis symptom outcomes in Chinese subjects.