Abdominal pain in children and symptoms of somatization disorder

Children seen in a multispecialty medical clinic for abdominalpain were divided into three groups: 21 with confirmed organicfindings related to the abdominal pain, 14 with confirmed organicfindings unrelated to the pain, and 108 whose physical examinationswere negative (the functional pain group). For children withfunctional abdominal pain (but not for the others) the numberof symptoms of somatization disorder (Briquet's syndrome) wassignificantly related to the chronicity of the child's condition.Children with functional pain and no prior complaint had a meanof 1.95 symptoms; those with complaints of less than 1 year'sduration, 2.21 symptoms; those with complaints of more thana year since age 6, 4.04 symptoms; and those with complaintsfor more than a year with onset prior to age 6 years, 4.55 symptomsfrom the Somatization Disorder list. Findings were interpretedas preliminary evidence for a distinct, chronic, polysymptomatichysterical disorder beginning in childhood.     

TNF revisited: TNF-independent antitumor activity in sera of mice sensitized with Propionibacterium acnes and challenged with lipopolysaccharide

Sera of mice sensitized with bacteria and subsequently challenged with lipopolysaccharide promote hemorrhagic necrosis of tumors in vivo and display cytotoxic activity against tumor cells in vitro, which has been attributed to the induction of tumor necrosis factor (TNF). Here, we describe the induction of a previously unrecognized antitumor activity in such sera, which is distinct from TNF but displays tumor-specific cytocidal activity in vitro as well as potent tumor-regressing activity in vivo. Biochemical analysis of this activity yielded a molecular mass of approximately 150 kDa, closely resembling a novel tumoricidal factor of murine macrophages (Mphi) termed MTC 170 (Mphi tumor cytotoxin, approximate molecular mass 170 kDa), which we have previously proposed to constitute a major effector pathway for the destruction of tumor cells by activated Mphi.     

Inhibitory interaction in the cat's lateral geniculate nucleus

Summary Spike activities of optic tract fibers and corresponding relay cells were recorded simultaneously in layers A and A₁ of the dorsal lateral geniculate nucleus of the cat. Light stimuli of various diameters were shone into the receptive field center of these unit pairs and their input/output ratios were determined. An increase of the stimulus size leads to an impairment of the input/output ratio in on-center and off-center relay cells. This suppressive effect has approximately the same latency as the excitatory response.Intracellular recordings suggest that the inhibitory effect of the surround is due to a postsynaptic process. Inhibitory postsynaptic potentials occur during and — under certain stimulus conditions —before the excitatory response. The short latency of these IPSPs suggests that they result from the activity of adjacent units with the same RF characteristics as the recorded neuron. This inhibitory input is not restricted to the RF periphery but may also be activated by stimulation within the RF center. Most neurons are also inhibited by units with antagonistic center responses.During the period of this research Ernst Pöppel held a training grant of the Stiftung Volkswagenwerk, Az. 11 1015.     

Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease

 Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD. Received: 15 February 1996 / Accepted: 2 October 1996     

Production of stable anti-digoxin Fv in Escherichia coli.

We have created a bacterial expression-export system and have used it to express (14 mg l-1) the variable region fragment (Fv) of an anti-digoxin antibody (26-10) in Escherichia coli. The expression-export plasmid contains a T7 promoter and the E. coli signal sequences ompA [Movva et al., J. biol. Chem. 255, 27-29 (1980)] and phoA [Inouye et al., J. Bacteriol. 149, 434-439 (1982)] fused to heavy chain (VH) and light chain (VL) variable region sequences to generate an artificial cistron. The 26-10 Fv protein made using this system was soluble, unlike many other expression systems which produce insoluble proteins in the form of inclusion bodies. The 26-10 VH and VL proteins were cleaved at their mature N-termini and exported into the bacterial periplasm where they could be easily extracted and affinity purified on ouabain-Sepharose. 26-10 Fv bound to digoxin with similar affinity and specificity as the whole 26-10 antibody (Ka for Fv, 1.3 x 10(9) M-1, Ka for IgG, 7 x 10(9) M-1). 26-10 Fv appears to be remarkably stable in comparison with other Fv fragments. The half-life for chain dissociation of 26-10 Fv was 48 hr compared to the reported 1.5 hr half-life of McPC603 Fv. We present the proton NMR spectra of the 26-10 Fv as preliminary evidence that this expression-export system can be used to facilitate the analysis of the solution structure of 26-10 Fv by NMR.     

Differences in airway remodeling between subjects with severe and moderate asthma

BACKGROUND: Airway remodeling in asthma comprises a range of structural changes. Several studies have suggested an association between these changes and disease severity. The relationship between the extent of remodeling and lung function is not well defined. OBJECTIVE: We sought to contrast the structural changes in the airways of well-defined groups of subjects with severe and moderate asthma and to correlate the extent of remodeling with disease severity. METHODS: Endobronchial biopsy specimens were obtained from 15 subjects with severe and 13 subjects with moderate asthma. Epithelial integrity, cell-layer areas, subepithelial fibrosis, and the distance between epithelial and airway smooth muscle (ASM) layers were measured by means of image analysis. Collagen was identified by using Van Giesen stain, and ASM was defined by using smooth muscle alpha-actin immunostaining. Specific immunostains were performed for the evaluation of RANTES, IL-8, and eotaxin expression as markers of ASM phenotype. RESULTS: ASM area was greater in subjects with severe (0.24+/- 0.03 mm(2)) than in subjects with moderate (0.05+/- 0.01 mm(2)) asthma (P<.001). The distance between the epithelial and ASM layers was less in the severe group (0.12+/- 0.01 mm) than in the moderate group (0.24+/- 0.02, P<.001). A trend toward greater subepithelial fibrosis in subjects with severe asthma did not reach statistical significance. IL-8 and eotaxin expression, but not RANTES expression, were increased in the ASM of subjects with severe asthma compared with in subjects with moderate asthma. CONCLUSION: Smooth muscle alteration is the key structural change that distinguishes severe from moderate asthma, and phenotypic change in ASM might contribute to the difficulty in obtaining adequate control in some subjects with severe asthma.     

Screening 34 Peanut Introductions for Allergen Content Using ELISA

Peanut is one of the most allergenic foods and reports of accidental ingestion of peanuts in unsuspected food are increasing. No information is available on the allergen content of peanut germplasm grown commercially and used in the food and confectionery industry. The objectives of this study were: (1) to determine the allergen contents of 34 peanut introductions (PI); and (2) to identify naturally occurring allergen-free and/or low or hypoallergenic peanuts germplasm. A basic ELISA protocol was utilized to detect the presence of antigens in the peanut lines using a pool of human sera from patients with documented history of peanut allergy. Two naturally occurring low, or hypo-allergenic germplasm were identified as PI 261942 and PI 338386. Both are Valencia market types with total allergen content significantly lower (P ≤0.05) than that of PI 119880 (0.550), PI 119876 (0.415) and PI 118991 (0.410) three Valencia market types and PI 262111 (0.485), a Virginia market type. No allergen-free PI was found. Allergen content of peanut lines from Bolivia and Paraguay were significantly (P ≤0.05) different to those from Venezuela. No significant difference was observed in the allergen content of the four market types.     

A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids

alpha-Methylacyl-CoA racemase (Amacr) deficiency in humans leads to sensory motor neuronal and liver abnormalities. The disorder is recessively inherited and caused by mutations in the AMACR gene, which encodes Amacr, an enzyme presumed to be essential for bile acid synthesis and to participate in the degradation of methyl-branched fatty acids. To generate a model to study the pathophysiology in Amacr deficiency we inactivated the mouse Amacr gene. As per human Amacr deficiency, the Amacr(-/-) mice showed accumulation (44-fold) of C27 bile acid precursors and decreased (over 50%) primary (C24) bile acids in bile, serum and liver, however the Amacr(-/-) mice were clinically symptomless. Real-time quantitative PCR analysis showed that, among other responses, the level of mRNA for peroxisomal multifunctional enzyme type 1 (pMFE-1) was increased 3-fold in Amacr(-/-) mice. This enzyme can be placed, together with CYP3A11 and CYP46A1, to make an Amacr-independent pathway for the generation of C24 bile acids. Exposure of Amacr(-/-) mice to a diet supplemented with phytol, a source for branched-chain fatty acids, triggered the development of a disease state with liver manifestations, redefining the physiological significance of Amacr. Amacr is indispensable for the detoxification of dietary methyl-branched lipids and, although it contributes normally to bile acid synthesis from cholesterol, the putative pMFE-1-mediated cholesterol degradation can provide for generation of bile acids, allowing survival without Amacr. Based upon our mouse model, we propose elimination of phytol from the diet of patients suffering from Amacr deficiency.