Low levels of immunoglobulin A in children with intrinsic asthma: a possible protection against atopy

Immunoglobulin A and G (IgA, IgG) serum concentrations were detected in children with nonallergic/intrinsic (36 children) or allergic/extrinsic asthma (43 children) and in age-matching control children (40 children). Asthmatic children with allergic asthma had lower IgA (1.36+/-0.54 g/L) and higher IgG (10.48+/-2.77 g/L) levels than the age-matching control children group (1.63+/-0.69 vs. 9.01+/-2.32 g/L). Children with nonallergic/intrinsic asthma had lower IgA (1.03+/-0.41 g/L) ( p = 0.004) and IgG (8.38+/-1.93 g/L) (p = 0.001) levels than the allergic/extrinsic asthma group (1.36+/-0.54 vs. 10.48+/-2.77 g/L). Low IgA levels were found in children with nonallergic/intrinsic asthma and high IgG levels were found in those children with allergic/extrinsic childhood asthma. The hypothesis is that the increased incidence of asthma in the population may be caused by a decrease in childhood infections (hygiene hypothesis). Frequent infections in early life boost the immune system, stimulating Th1-type response in young children and reducing the risk of atopic diseases. Our hypothesis is that low IgA (and/or IgG) levels in our patients might be responsible for infection development among those children with nonallergic/intrinsic asthma. These infections stimulate the normal development of immune system in young children, reducing risk of atopy, so that those children do not get allergic/extrinsic childhood asthma. Intrinsic childhood asthma=nonallergic (nonatopic) childhood asthma. Extrinsic childhood asthma=allergic (atopic) childhood asthma.     

Effect of prostaglandin E2 and 3-morpholinosydnonimine (SIN-1) on arachidonic acid metabolism in fMLP-stimulated rat neutrophils and on thrombin-induced human platelet aggregation

The effects of prostaglandin (PG) E₂ and the nitric oxide (NO) donor SIN-1 on leukotriene (LT) release from formyl-methionyl-leucyl-phenylalanine (fMLP) (100 nM)-stimulated rat peritoneal neutrophils (RPN) and on thrombin-induced aggregation of washed human platelets were investigated. Both PGE₂ (1–100 nM) and SIN-1 (30–300 M) inhibited release of LTB₄ and cysteinyl-LT from RPN in a concentration-dependent manner. The combined effects of PGE₂ and SIN-1 were not greater than expected by summation. On the other hand, the inhibitory effect of SIN-1 (0.5 or 1.0 M) on platelet aggregation was potentiated by PGE₂ (0.3–5 M) in a concentration-dependent manner, while PGE₂ alone in the concentrations used had only marginal effects. The results suggest differential regulation of platelet and leukocyte functions by the mediators PGE₂ and NO, which could be relevant for various physiological and pathophysiological conditions.     

nm23-H1 expression in squamous cell carcinoma of the head and neck

Archival material from 47 patients with primary squamous cell carcinoma of the head and neck (SCCHN) was studied immunohistochemically for the presence of nm23-H1 protein. Our data indicate that nm23-H1 protein expression is a common event in SCCHN and that there is a trend toward correlation of increased expression of nm23-H1 with increasing tumor size (p = 0.072). The results also show that when adjusting for age and cause of death, there tended to be an inverse relationship between overall survival and the expression of nm23-H1 gene in the primary tumor (p = 0.088).     

Can Sensitized Lymphocytes Retain Reactivity to Inner Ear Antigens After Retrieval From Frozen Storage?

Immune inner ear disease results in rapidly progressive, bilateral sensorineural hearing loss and is one of the few forms of sensorineural hearing loss that can be treated medically. The purpose of this study is to identify and preserve several populations of sensitized lymphocytes from patients with immune inner ear disease as a first step toward cloning autoreactive T cells, in order to study the pathogenesis of disease. Lymphocytes from four patients with high reactivity (stimulation index of 2.5 or greater) were placed in frozen storage. At 8 to 14 months they were thawed and restimulated. All four samples were viable. Two reacted again to inner ear homogenate, but with different intensities. Some lymphocytes sensitized to inner ear antigens can retain reactivity after frozen storage. This methodology may be useful to clone highly reactive T cells.     

Prognostic Indicators for Squamous Cell Carcinoma of the Oral Cavity: A Clinicopathologic Correlation

Fifty-three patients with T1 squamous cell cancer of the floor of mouth and ventral surface of the tongue with a known clinical outcome were retrospectively analyzed and arbitrarily divided into “aggressive” and “nonaggressive” groups based on their clinical behavior. Various host and tumor factors were then evaluated in an attempt to determine whether the tumor behavior could have been predicted. The paraffin-embedded tumor specimens were evaluated for tumor differentiation, tumor thickness and tumor invasion, microvessel density, and p53 expression. In addition, a composite morphologic grading score was obtained by combining cell differentiation, nuclear polymorphism, mitosis activity, depth of infiltration, type of infiltration, and lymphatic infiltration. No single technique appeared capable of identifying “aggressive” behavior, although possibly an evaluation of composite factors might show promise in the future.     

Animal and human dentin microstructure and elemental composition

Animal teeth are a common model in studies on dentin adhesive materials. The aim of this study was to compare microstructural parameters (density and diameter of dentinal tubules (DT), peritubular dentin (PTD) thickness, PTD and intertubular dentin (ITD) surface area) and chemical characteristics of canine, porcine, equine, and human root dentin. The middle layers of dentin were harvested just below a cemento-enamel junction from incisors and investigated by means of scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDXS). SEM evaluation of the specimens revealed, that porcine dentin shared most similarities with human dentin. When comparing the density of DTs, canine dentin was also found to be similar to human dentin. Elemental composition of the root dentin did not differ significantly in porcine, equine and human dentin, but in canine dentin higher magnesium value in PTD compared to ITD was found. It is known that microstructural and chemical characteristics affect the strength of the adhesive bonds created among restorative materials and dentin. According to the results of this study, porcine dentin seems to be the most appropriate model to study dental materials to be used in human restorative dentistry.     

Role of prostaglandin and thromboxane biosynthesis in gastric necrosis produced by taurocholate and ethanol

The effects of a new selective inhibitor of thromboxane biosynthesis, OKY-1581, and a potent inhibitor of cyclooxygenase, indomethacin, on gastric mucosal lesions induced by taurocholate or ethanol and mucosal generation of prostaglandins have been studied in rats. OKY-1581 prevented, dose dependently, the formation of taurocholate- but not ethanol-induced gastric necrosis, and this effect was accompanied by an increase in gastric mucosal generation of prostaglandin E2 and I2-like activity and a reduction in the thromboxane generation during platelet aggregation. OKY-1581 enhanced the cytoprotective action of "mild" irritants such as 5 mM taurocholate against gastric damage by 100 mM taurocholate, whereas indomethacin produced opposite effects. This study indicates: (1) the inhibition of thromboxane biosynthesis results in increased generation of prostaglandins which seems to contribute to the gastric mucosal integrity and, (2) thromboxanes may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions.     

D-14 Monoclonal antibody to carcinoembryonic antigen: immunohistochemical analysis of formalin-fixed,paraffin-embedded human colorectal carcinoma,tumors of non-colorectal origin and normal tissues

Summary The reactivity of D-14 monoclonal antibody (mAb) to a specific epitope of carcinoembryonic antigen (CEA) was evaluated on formalin-fixed, paraffin-embedded tissues. A total of 52 normal tissues, 90 colorectal carcinomas and 127 non-colorectal neoplasms were tested using the peroxidase/antiperoxidase technique. D-14 mAb did not react with normal tissues apart from producing a weak staining of normal colonic glands immediately adjacent to the neoplastic structures. All 61 primary and 29 metastatic colorectal carcinomas expressed the carcinoembryonic antigen. However, there was considerable heterogeneity in cellular antigen expression in both primary and metastatic colorectal carcinomas with 10%–99% of tumor cells staining. Of 22 stomach adenocarcinomas, 14 were also immunoreactive, as were 2 of 5 pancreatic carcinomas. Only 6 of 100 neoplasms of non-gastrointestinal origin expressed weak to moderate immunoreactivity. In 7 cases, colorectal micrometastases not recognized in conventional hematoxylin and eosin slides could be identified with D-14 mAb. The specificity of this antibody could be used in differentiating colorectal carcinomas from other types of tumors, including adenocarcinoma from other sites.This paper was presented at the 1989 Annual Meeting of the American Association for Cancer Research Inc., San Francisco, California     

The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes

CONTEXT: Endocrine defensive mechanisms provide for energy supply during hypoglycemia. Intramyocellular lipids (IMCL) were recently shown to contribute to energy supply during exercise. OBJECTIVE: The objective of this study was to assess the contribution of IMCL compared with lipolysis and endogenous glucose production (EGP) to insulin-mediated hypoglycemia counterregulation in patients with type 1 diabetes mellitus (T1DM). DESIGN AND SETTING: This was a prospective explorative study performed in a university research facility. PARTICIPANTS: Six well-controlled T1DM (age, 29 +/- 4 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 6.3 +/- 0.1%) and six nondiabetic humans (controls; age, 28 +/- 2 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 5.1 +/- 0.1%) were studied. INTERVENTIONS: We performed 240-min hypoglycemic (approximately 3 mM)-hyperinsulinemic (0.8 mU/kg x min) clamps on separate days to measure: 1) systemic lipolysis ([2H5]glycerol turnover), EGP ([6,6-(2)H2]glucose), and local lipolysis in abdominal s.c. adipose tissue and gastrocnemius muscle (microdialysis); and 2) IMCL (by 1H nuclear magnetic resonance spectroscopy) in soleus and tibialis anterior muscle. MAIN OUTCOME MEASURES: The main outcome measures were changes in IMCL during prolonged hypoglycemia. RESULTS: At baseline, EGP, glycerol turnover, and IMCL were not different between the groups. During hypoglycemia, hormonal counterregulation was blunted in T1DM (peak: glucagon, 68 +/- 4 vs. 170 +/- 37 pg/ml; cortisol, 16 +/- 2 vs. 24 +/- 2 microg/dl; epinephrine, 274 +/- 84 vs. 597 +/- 212 pg/ml; all P < 0.05 vs. control). T1DM had approximately 50% lower EGP (4.6 +/- 0.6 vs. 10.9 +/- 0.5 micromol/kg x min; P < 0.005), but approximately 40% higher glycerol turnover (374 +/- 21 vs. 272 +/- 19 micromol/kg x min; P < 0.01). Glycerol concentrations in muscle (T1DM, 302 +/- 22 control, 346 +/- 17 micromol/liter) and adipose tissue (264 +/- 25 vs. 318 +/- 25 micromol/liter) did not differ between groups. IMCL in soleus and tibialis anterior muscle did not change from baseline during hypoglycemia. CONCLUSIONS: In well-controlled T1DM, impaired hypoglycemia counterregulation is associated with decreased glucose production and augmented whole body lipolysis, which cannot be explained by either hydrolysis of muscle triglycerides or increased abdominal s.c. adipose tissue lipolysis.