Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives

Autoimmunity to cytoskeletal protein tropomyosin (TM) has been demonstrated in UC. However, the TM isoforms involved in this IgG-mediated autoimmune response in UC and the possible presence of serum IgG antibodies against TM (hTMs IgG) in unaffected UC relatives are unknown. The aim of this study was to investigate the human TM (hTM) isoforms recognized by serum IgG from UC and to explore whether hTM IgG antibodies are present in healthy UC relatives. We studied 33 UC patients with 58 unaffected relatives, 31 Crohn's disease (CD) patients with 31 unaffected relatives and 20 controls (C). Serum IgG against four recombinant hTM isoforms (hTM1, 2, 3, 5) were tested by ELISA. p-ANCA were tested by ELISA and immunofluorescence. Serum hTM1 and hTM5 IgG were higher in UC patients than in CD and C (P < 0.005). Among UC patients 52% were seropositive for hTM1 and 64% for hTM5 (P < 0.001 versus CD and C). In UC, hTM5 IgG were higher in p-ANCA⁺ than in ANCA^? patients (P = 0.04). In UC relatives hTM1 IgG were higher than in CD relatives and C (P < 0.01). UC relatives were more frequently seropositive for hTM1 than hTM5 IgG (P = 0.001), while probands were more frequently seropositive for hTM5 IgG (P = 0.008). We conclude that autoimmunity to hTM1 and hTM5 is a feature of UC, while hTM1 IgG differentiate UC relatives from controls. A genetic susceptibility to immune recognition of hTM isoforms in UC is suggested.     

MATERNAL HLA CLASS II ALLOGENOTYPES ARE MARKERS FOR THE PREDISPOSITION TO FETAL LOSSES IN FAMILIES OF WOMEN WITH UNEXPLAINED RECURRENT FETAL LOSS

The HLA allogenotypes DRl/Br, DR3 and DR10 (entitled risk HLA markers) have been reported as being genetic markers for the predisposition to experience unexplained recurrent fetal losses. The aim of the study was to determine whether the putative risk HLA markers might also be markers for the risk of pregnancy loss in sisters and wives of brothers of women with unexplained recurrent fetal losses. Information concerning pregnancy outcomes among the relatives of 146 consecutive women with unexplained recurrent fetal losses was collected. Ninety-five of the full sisters, 69 of the full brothers and 50 of the wives of the brothers were HLA typed. Sisters who had experienced at least one previous pregnancy loss (affected women) shared more HLA haplotypes with the proband than unaffected sisters, when the proband was positive for the risk markers (P= 0.02). More affected than unaffected sisters and brothers’ wives were positive for the risk markers (P < 0.005 and P < 0.03; respectively). The lowest estimate of the odds ratio for experiencing pregnancy loss among sisters and brothers’ wives who were positive compared with those negative for the risk markers was 3.5 (95% credible interval = 1.9-5.8). It is concluded that maternal DRl/Br, DR3 and DR10 allogenotypes seem to be genetic markers for the risk of pregnancy loss among relatives of women with unexplained recurrent fetal losses. The pattern of inheritance suggests a polygenic mode of inheritance with alleles linked to the risk HLA markers interacting with non-HLA linked genes expressed on the fetus or the trophoblast.     

Gene Polymorphism of Interleukin-4, Interleukin-4 Receptor and STAT6 in Children with Atopic Dermatitis in Taif,Saudi Arabia

Aim of study: This work was performed to evaluate the level of IL-4, and to clarify the role of IL-4 gene polymorphism at position cytosine –590-to-thyamine (C-590T), IL-4Rα gene polymorphism at position adenine +4679-to-guanine (A+4679G) [isoleucine-50-valine (I50V)] and STAT6 gene polymorphism at position guanine 2964-to-adenine (G2964A) in Saudi children with non-atopic dermatitis (non-AD) and atopic dermatitis (AD) to identify their role in the pathogenesis of these diseases.

Subjects and methods: This study included 150 children: 50 healthy children as controls, 50 with non-AD, and 50 with AD. They were subjected to full clinical examination, complete blood picture, skin prick test, and determination of serum interleukin-4 (IL-4) and total immunoglobulin-E (IgE) levels. Detection of interleukin-4 gene (C-590T), interleukin-4 receptor alpha gene (A+4679G) (I50V), and STAT6 gene (G2964A) polymorphisms were performed by PCR-based restriction fragment length polymorphism (PCR-RFLP).

Results: There was a significant (P < 0.01) association between genotype and allele frequencies of IL-4Rα (A+4679G) (I50V) polymorphism in the AD group (but not non-AD group). Moreover, there was a significant association between genotype and allele frequencies of the STAT6 (G2946A) polymorphism in the non-AD (P < 0.05) and AD (P < 0.01) groups. On the other hand, there was no significant association between genotype and allele frequencies of the (C-590T) polymorphism in the non-AD group and AD group. There was a significant (P < 0.001) higher total IgE level in patients compared to the controls. Moreover, the mean values of total IgE were significantly different among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively, in all the studied groups. On the other hand, there was no significant difference of serum IL-4 levels among all the studied patients, or among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively.

Conclusion: IL-4Rα gene (I50V) and STAT6 gene (G2964) polymorphisms may play a role in development of eczema; however, the IL-4 gene polymorphism (C-590T) had no relationship with susceptibility to the disease among Saudi children.     

Floating density of hepatitis C virus particles and response to interferon treatment

Hepatitis C virus (HCV) particles can be classified into two major fractions according to their floating density in serum. However, the genomic heterogeneity of each fraction and the relationship between this viral characteristic and interferon (IFN) response in patients with chronic hepatitis are not known. In this study, floating density and single strand conformation polymorphism (SSCP) of the hypervariable region 1 (HVR1) of HCV were examined in 16 patients with chronic hepatitis prior to IFN treatment. The ratio of HCV RNA titers in the top (T) and bottom (B) fractions, or T:B ratio, was 10:1 in 4 patients, 1:1 in 7, and 1:10 in 5. Three of the 4 patients with a 10:1 ratio showed a sustained response to IFN, while none of the 5 patients with a 1:10 ratio demonstrated a sustained response (P < 0.05). All 4 patients with a 10:1 ratio had 1 or 2 SSCP bands, and 4 of the 5 patients with a 1:10 ratio had 4 or 5 bands (P < 0.01). Furthermore, the number of SSCP bands in the top fraction from 6 sustained responders (1.8 ± 0.3) was significantly smaller than from 10 non sustained responders (4.1 ± 0.8) (P < 0.05). Thus, patients with a high T:B ratio and low heterogeneity in HVR1 demonstrated sustained responses to IFN, while those with low T:B ratios and high heterogeneity did not. J. Med. Virol. 55:12–17, 1998. © 1998 Wiley-Liss, Inc.     

Correction of Th1-dominant Cytokine Profiles by High-dose Dexamethasone in Patients with Chronic Idiopathic Thrombocytopenic Purpura

To investigate the possible correcting of T helper (Th) cytokine profiles by high-dose dexamethasone (HD-DXM) therapy in chronic idiopathic thrombocytopenic purpura (ITP) with active disease, we determined the plasma levels of IFN-γ, IL-2, IL-4, IL-10, and TGF-β1 in 52 patients before and after oral administration of 40 mg/day DXM for four consecutive days. The cytokine levels were measured by enzyme-linked immunosorbent assay. The results showed that initial responses were reached in all patients and sustained response (SR) rate is 46.15%. The pretreatment plasma levels of both IFN-γ and IL-2 were significantly increased and those of IL-4, IL-10, and TGF-β1 significantly decreased, compared with those of the normal controls (P < 0.01), indicating a Th1-dominant cytokine profile typically found in ITP. After HD-DXM treatment, IFN-γ and IL-2 were decreased (P < 0.01), whereas IL-4 and IL-10 were increased (P < 0.05). There was no significant difference between the HD-DXM-treated patients and the normal controls (P > 0.05). TGF-β1 was also increased (P < 0.01) after HD-DXM treatment, but still lower than that of the normal controls (P < 0.05). During following-up, the cytokine profiles in the SRs remained stable compared to the posttreatment level (P > 0.05), but IFN-γ and IL-2 levels raised up, and IL-4, IL-10, and TGF-β1 levels reduced again in the relapsed patients (P < 0.01). Our data demonstrate that HD-DXM is an effective initial therapy for ITP, and the Th1 cytokine dominance could be corrected by HD-DXM.     

Exploratory genotype–phenotype correlations of facial form and asymmetry in unaffected relatives of children with non‐syndromic cleft lip and/or palate

Family relatives of children with nonsyndromic cleft lip with or without cleft palate (NSCL/P) who presumably carry a genetic risk yet do not manifest overt oral clefts, often present with distinct facial morphology of unknown genetic etiology. This study investigates distinct facial morphology among unaffected relatives and examines whether candidate genes previously associated with overt NSCL/P and left–right body patterning are correlated with such facial morphology. Cases were unaffected relatives of individuals with NSCL/P (n = 188) and controls (n = 194) were individuals without family history of NSCL/P. Cases and controls were genotyped for 20 SNPs across 13 candidate genes for NSCL/P (PAX7, ABCA4‐ARHGAP29, IRF6, MSX1, PITX2, 8q24, FOXE1, TGFB3 and MAFB) and left–right body patterning (LEFTY1, LEFTY2, ISL1 and SNAI1). Facial shape and asymmetry phenotypes were obtained via principal component analyses and Procrustes analysis of variance from 32 coordinate landmarks, digitized on 3D facial images. Case–control comparisons of phenotypes obtained were performed via multivariate regression adjusting for age and gender. Phenotypes that differed significantly (P < 0.05) between cases and controls were regressed on the SNPs one at a time. Cases had significantly (P < 0.05) more profile concavity with upper face retrusion, upturned noses with obtuse nasolabial angles, more protrusive chins, increased lower facial heights, thinner and more retrusive lips and more protrusive foreheads. Furthermore, cases showed significantly more directional asymmetry compared to controls. Several of these phenotypes were significantly associated with genetic variants (P < 0.05). Facial height and width were associated with SNAI1. Midface antero‐posterior (AP) projection was associated with LEFTY1. The AP position of the chin was related to SNAI1, IRF6, MSX1 and MAFB. The AP position of the forehead and the width of the mouth were associated with ABCA4–ARHGAP29 and MAFB. Lastly, facial asymmetry was related to LEFTY1, LEFTY2 and SNAI1. This study demonstrates that, genes underlying lip and palate formation and left–right patterning also contribute to facial features characteristic of the NSCL/P spectrum.     

Eosinophilia in patients infected with the human immunodeficiency virus

The prevalence and significance of peripheral blood eosinophilia in patients infected with the human immunodeficiency virus (HIV) were evaluated. Fifteen of 119 consecutive patients had absolute eosinophil counts of > 450/mm³. During a mean follow-up period of 419 days eosinophilia could be identified as secondary to a parasitic infection in only one patient. Correlation with disease stage showed a higher rate of advanced disease in patients with absolute eosinophilia. In a multivariate regression analysis, only low CD4+ cell counts, not the CDC disease stage or the use of antiretroviral therapy or primary prophylaxis, contributed significantly to the prevalence of eosinophilia. It is concluded that expen-sive laboratory investigations in asymptomatic patients with advanced-stage HIV disease are neither necessary nor cost effective.     

Cephalometric analysis of families with dominantly inherited Crouzon syndrome: An aid to diagnosis in family studies

Crouzon syndrome (CS) is an autosomal dominant condition comprising orbital proptosis, midfacial hypoplasia, premature sutural synostosis, and altered proportions of bone lengths in the hands. In families the CS trait is highly variable. Several cases of affected sibs born to unaffected parents have been explained by germinal mosaicism. We hypothesized that cephalometric and metacarpophalangeal analysis may help to classify affected and unaffected subjects within families when clinical diagnosis is difficult. Posterior-anterior and lateral cephalometric radiographs and hand films were taken of 10 CS patients and 18 unaffected relatives. Sixty-two craniofacial and 19 hand linear and angular measurements were made on each subject and standardized by conversion to z-scores using published normal standards. Ten craniofacial variables were selected for use in a stepwise forward discriminant function analysis to develop an equation which could be used to discriminate CS patients from normal subjects. A two-group discriminant function using four craniofacial variables and one hand variable correctly classified the CS patients and relatives 100 % of the time. The results suggest that relatively few facial variables are needed to differentiate most cases of CS but the addition of one or more hand variables may increase the sensitivity. DNA testing is necessary to adequately demonstrate incomplete penetrance in CS, but pretesting subjects for molecular studies using these methods may improve results. Am. J. Med. Genet. 77:405–411, 1998. © 1998 Wiley-Liss, Inc.     

Elevated Epstein-Barr virus seroreactivity among unaffected members of families with nasopharyngeal carcinoma

Serum antibodies to Epstein–Barr virus (EBV) antigens can be used to predict the risk of nasopharyngeal carcinoma (NPC). To investigate whether EBV seropositivity rates were higher among healthy family members from multiplex and sporadic families with NPC (i.e., families with multiple or single cases) compared to the general population, a study was conducted on 2,665 unaffected individuals from 140 multiplex and 413 sporadic families. The titers of the IgA antibody to the EBV capsid antigen (VCA‐IgA) were compared to those of 904 controls from the general population. The VCA‐IgA titer was correlated among sibling pairs to a high significance in both family types (P < 0.0001 and P = 0.0005 for the multiplex and the sporadic families, respectively); parent–offspring pairs also showed significant correlation (P < 0.0001 and P = 0.0002, respectively); and spouse pairs were correlated, but at lower significance levels (P = 0.0790 and P = 0.0040, respectively). When compared to the controls, among first‐degree relatives in the multiplex families, the age‐ and gender‐adjusted odds ratio (OR) was 2.06 (95% confidence interval 1.56–2.71), 3.55 (2.24–5.64), and 2.25 (1.57–3.23) for siblings, parents, and children, respectively. In the sporadic families, the adjusted OR was 1.55 (1.21–2.00) and 2.08 (1.51–2.86) for siblings and parents, respectively. The adjusted P‐value of spouses lost significance in the multiplex families, but remained significant in the sporadic families (P = 0.0146). In conclusion, EBV seropositivity rates were elevated among unaffected family members in both multiplex and sporadic families with NPC. J. Med. Virol. 83:1792–1798, 2011. © 2011 Wiley‐Liss, Inc.     

Changes in plasma concentrations of interleukin-6 and interleukin-1 receptor antagonists in response to adrenaline infusion in humans

To investigate the possible role of adrenaline in the response of interleukin (IL)-6 and IL-1 receptor antagonists (ra) to extreme physiological conditions such as trauma and exercise, we examined the concentrations in the plasma of these cytokines during an adrenaline infusion. Given the fact that HIV infected patients have elevated levels of IL-6 in plasma, 12 HIV seropositive subjects and 6 HIV seronegative control subjects received a 1-h adrenaline infusion. Baseline concentrations of IL-6 and IL-1ra were higher in the HIV patients compared with the controls (P < 0.05 and P < 0.01, respectively), being most pronounced in the untreated subgroup of HIV infected patients (n=6). The plasma concentration of adrenaline had increased 24-fold after 15 min of adrenaline infusion. The plasma concentration of IL-6 had increased by two- to threefold after 45 min of adrenaline infusion (P < 0.01) and was still elevated 1 h after the infusion had ended (P < 0.001 and P < 0.05 in controls and HIV infected patients, respectively). The plasma concentration of IL-1ra had increased two- to threefold 1 h after ceasing the adrenaline infusion (P < 0.05 and P < 0.01 in controls and HIV infected patients, respectively). The relative increase in the cytokine levels was similar in controls and HIV infected patients. Thus, HIV infection did not influence the effect of adrenaline on IL-6 and IL-1ra. The present study supports the existence of a relationship between the plasma concentration of adrenaline and IL-6. It is possible that an increased adrenaline concentration in plasma induces a continued de novo synthesis of IL-6, thereby increasing plasma IL-6 in a time–dose dependent manner. Accepted: 16 April 2000     

A genome-wide search for schizophrenia susceptibility genes

We completed a systematic genome-wide search for evidence of loci linked to schizophrenia using a collection of 70 pedigrees containing multiple affected individuals according to three phenotype classifications: schizophrenia only (48 pedigrees; 70 sib-pairs); schizophrenia plus schizoaffective disorder (70 pedigrees; 101 sib-pairs); and a broad category consisting of schizophrenia, schizoaffective disorder, paranoid or schizotypal personality disorder, psychosis not otherwise specified (NOS), delusional disorder, and brief reactive psychosis (70 pedigrees; 111 sib-pairs). All 70 families contained at least one individual affected with chronic schizophrenia according to DSM-III-R criteria. Three hundred and thirty-eight markers spanning the genome were typed in all pedigrees for an average resolution of 10.5 cM (range, 0–31 cM) and an average heterozygosity of 74.3% per marker. The data were analyzed using multipoint nonparametric allele-sharing and traditional two-point lod score analyses using dominant and recessive, affecteds-only models. Twelve chromosomes (1, 2, 4, 5, 8, 10, 11, 12, 13, 14, 16, and 22) had at least one region with a nominal P value <0.05, and two of these chromosomes had a nominal P value <0.01 (chromosomes 13 and 16), using allele-sharing tests in GENEHUNTER. Five chromosomes (1, 2, 4, 11, and 13) had at least one marker with a lod score >2.0, allowing for heterogeneity. These regions will be saturated with additional markers and investigated in a new, larger set of families to test for replication. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:364–376, 1998. © 1998 Wiley-Liss, Inc.     

Cytogenetic studies of familial and sporadic Alzheimer disease

We present cytogenetic findings in 7 familial and 5 sporadic Alzheimer disease (AD) patients and 34 unaffected relatives, spouses, and normal controls. Our study was prompted by reports of increased chromosome abnormalities in patients and family members at risk for AD. Coded peripheral blood chromosome preparations were evaluated for aneuploidy, aberration rates, and banding patterns. Statistical analyses of our results showed no increase in aneuploidy or aberrations in AD patients, their relatives, or normals. Chromosome loss or gain in aneuploid cells was not specific except in two individuals. These two older persons studied, one with AD and one unaffected, were observed to have increased sex chromosome aneuploidy. This finding was attributed to aging and was not considered to be an effect of AD.     

Interleukin-18 and its three gene polymorphisms relating to allergic rhinitis

The study aimed to examine an association of three different single nucleotide polymorphisms (SNPs) of the IL-18 gene (−607 C/A, −137 G/C and −133 C/G) on chromosome 11q22 with allergic rhinitis (AR). Genotyping for the SNPs was performed using 539 patients with AR and 312 healthy control volunteers. Positivity to the skin prick test for the fungus Alternaria sp. in patients with AR, and IgE levels according to particular genotypes of selected SNPs, were also determined. There were no significant differences in the distribution of single IL-18 alleles or genotypes between controls and AR patients. However, frequencies of combined IL-18 genotypes arising from combinations of the three common polymorphisms (−607, −137 and −133) were significantly different between both groups (P = 0.009, P _corr < 0.05, OR = 5.35, 95% CI: 1.9–15.2). There was a marginally significant association of the IL-18–607 variant with IgE levels (P = 0.05) in patients, but not in the case of the other SNPs. Patients allergic to Alternaria, but not those allergic to other antigens, showed a significant association with the IL-18–607 polymorphism (P = 0.0037, P _corr < 0.05). Results suggest that IL-18 gene variants may be one of the factors participating in the pathogenesis of AR or its intermediary phenotypes.     

Periparturient rise in fecal egg counts associated with prolactin concentration increase in French Alpine dairy goats

Previous data on periparturient relaxation of immunity during gastrointestinal nematode infection in goats are scarce and conflicting; one study carried out in fiber (Angora) goats showed a positive association of fecal egg counts with prolactin concentrations around parturition, whereas the two other available studies dealing with dairy goats, gave divergent results. The objectives of the study were thus to assess the occurrence of a periparturient rise in fecal egg counts in dairy goats and to examine a possible relationship between the level of milk production and the intensity of the periparturient rise. A total of 28 French Alpine grazing dairy goats naturally infected with Teladorsagia, Trichostrongylus, and Oesophagostomum were allocated into two groups according to their reproductive status; group 1 (n = 7) consisted of nonpregnant lactating animals in the 3^rd month of lactation, whereas group 2 (n = 21) was composed of dry goats at 6 weeks before term. Fecal egg counts, pepsinogen and phosphate blood concentrations, blood eosinophil counts, and prolactin concentrations were individually monitored at weekly intervals for 12 weeks (from midwinter to early spring). The mean fecal egg counts were significantly higher in pregnant goats during the 2 weeks before (668 versus 242 eggs per gram of feces (epg), P < 0.05) and the 2 weeks after (962 versus 279 epg, P < 0.01) parturition as compared with nonpregnant lactating animals. No significant difference was seen in the composition of larval cultures between the two groups of animals, with Oesophagostomum infective larvae being found predominantly, particularly at the time of parturition. Pepsinogen and phosphate concentrations as well as blood eosinophil counts were similar between the two groups throughout the survey and indicated a moderate larval challenge. The mean prolactin concentration measured in pregnant goats was significantly higher (P < 0.01) at the time of parturition (298 versus 130 ng ml⁻¹) and at 4 weeks after parturition (387 versus 193 ng ml⁻¹) than that determined in nonpregnant animals. Furthermore, a significant correlation (r _s = 0.30, df = 79; P < 0.01) between fecal egg counts and prolactin concentrations was recorded for the pregnant goats during the 4-weeks period around parturition. Received: 2 April 1998 / Accepted: 8 June 1998     

T-Helper 1, T-Helper 2, and T-Regulatory Cytokines Gene Polymorphisms in Irritable Bowel Syndrome

Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position −590, IL-4 TT genotype at position −33, and IL-10 GA genotype at position −1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (−330, +160) GT haplotype (P = 0.002), IL-4 (−1098, −590, −33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.     

Expression of interferon alpha/beta receptor in the liver of chronic hepatitis C patients

Interferon (IFN) demonstrates antiviral activity by binding to receptors on the cell surface. Expression of the IFN receptor in hepatocytes may be directly associated with a hepatitis C virus (HCV) infection and the response to IFN therapy. A competitive PCR method was developed to measure IFN alpha/beta (α/β) receptor mRNA in liver samples obtained by needle biopsy. Thirty-one patients with chronic hepatitis C (21 without cirrhosis, 10 with cirrhosis) and six normal subjects were used. Eighteen of the 21 patients without cirrhosis received the IFN therapy. Competitive PCR was carried out using IFN α/β receptor gene-specific primers and a specific competitor. Expression of the receptor was detected in all liver samples. There was no association between the expression level and serum alanine aminotransferase level, serum (2′–5′) oligo (A) synthetase level, amount of serum HCV RNA, or HCV genotype. The expression level in patients with chronic hepatitis was significantly higher than that in normal livers (P < 0.05) and in cirrhotic livers (P < 0.01). Seven of the 18 patients treated with IFN demonstrated a sustained response to IFN (sustained responders), and the remaining 11 did not (nonsustained responders). The expression level of IFN α/β receptor mRNA in the sustained responders was significantly higher than that in the nonsustained responders (P < 0.01). Thus, the expression of IFN α/β receptor mRNA may be one of the host factors influencing the response to IFN therapy. J. Med. Virol. 56:217–223, 1998. © 1998 Wiley-Liss, Inc.     

Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro‐oesophageal reflux disease on oesophageal biopsy material

Aims: Eosinophil infiltration of the oesophageal epithelium is the cardinal pathomorphological finding in eosinophilic oesophagitis (EO), but gastro‐oesophageal reflux disease (GORD) is also associated with increased eosinophils. The aim was to compare histological parameters for the diagnosis of EO versus GORD on routinely taken biopsy specimens. Methods and results: One hundred and five routine biopsy specimens with EO (n = 62), GORD (n = 24) and probable EO (n = 19) from 74 patients (52 men, 22 women; mean age 43.7 years) were analysed for numbers of eosinophils, mast cells, degranulation and qualitative changes of oesophageal epithelium using immunohistochemistry with monoclonal antibodies against eosinophil peroxidase and eosinophil major basic protein and mast cell tryptase. Eosinophil infiltration was significantly higher in EO than in GORD both on haematoxylin and eosin staining (54.8 versus 9.1; P < 0.05) and immunohistochemistry (77.5 versus 24.7; P < 0.05). Eosinophil degranulation was significantly more intense in EO than in GORD (1.16 versus 0.41; P < 0.05). Furthermore, eosinophilia‐codependent secondary qualitative changes of squamous epithelium in EO were generally more extensive than those in GORD. Conclusions: Histological differential diagnosis of EO and GORD should be based on eosinophil counts, secondary morphological changes of eosinophils and oesophageal squamous epithelium, especially in cases suspicious of EO.     

Determination of IL-1 and IL-6 Levels in Human Embryo Culture-Conditioned Media

PROBLEM: The aim of this study was to evaluate the presence of interleukin-1 (IL-1) and IL-6 in 24-hour human embryo culture-conditioned media (HECCM) and to find any embryo-related factor(s) to predict pregnancy during IVF procedure. METHOD: IL-1β and IL-6 levels were measured in 36 samples of HECCM and 17 cell culture media that had not been exposed to embryos, which were used as controls. Both cytokine levels were measured by the ELISA technique, using commercially available kits. RESULTS AND CONCLUSIONS: We found an average IL-1β level ± SEM of 82 ± 4 pg/ ml (n=11) in HECCM from viable pregnancies and a significantly lower value, 14 ± 2 pg/ ml (n=25, P<0,001), in HECCM from embryos that did not lead to viable pregnancies. In control media the average IL-1β level was 11 ± 1 pg/ml (n=17), (P <0.001 vs. HECCM from viable pregnancies). In contrast IL-6 levels were undetectable in all samples analyzed. Judging by our results we suggest that measurement of IL-1 level in HECCM could be a useful parameter for predicting implantation in techniques of assisted reproduction.     

Association of an apolipoprotein CII allele with familial dementia of the Alzheimer type

In order to identify the genetic locus responsible for familial dementia of the Alzheimer type (DAT), we are studying 10 families in which DAT appears to be inherited as an autosomal dominant trait. Genotypes for a TaqI restriction fragment length polymorphism (RFLP) at the apolipoprotein CII locus were determined for the following groups: affected and unaffected DAT family members, DAT subjects with no family history of the disease, and normal control subjects. The control group included 103 individuals from our study and 123 from the study of Wallis et al. (Hum. Genet., 68 (1984) 286). The frequency of the TaqI fast (F) allele in the affected familial DAT subjects (0.64 ± 0.08) differed significantly from that for the control group (0.39 ± 0.02) (Z = 2.87, P <0.005). In contrast, the F-allele frequency for the unaffected family members was 0.31 ± 0.09, which was similar to that of the combined control group (Z = 0.78, P > 0.40). Subsequently, genotypes were determined for two other polymorphisms at the Apo CII locus: a BanI RFLP and a Bgll RFLP. For these two polymorphisms, the allele frequencies for the familial DAT subjects differed from the unaffected control groups but the differences were smaller and not statistically significant. These data suggest a previously unrecognized association between the Apo CII TaqI F-allele and familial DAT.     

Increased eosinophil activity in acute Plasmodium falciparum infection—association with cerebral malaria

To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM (geometric mean (95% confidence interval) 8.5 ng/ml (6.8–10.7 ng/ml)) than in SA (4.7 ng/ml (3.0–7.5 ng/ml)) and UM patients (4.3 ng/ml (3.6–5.3 ng/ml), P < 0.001). A similar pattern was found for EPX. It thus appears that the low eosinophil counts may be due to tissue sequestration and destruction rather than decreased production. The plasma levels of the granule proteins correlated with levels of tumour necrosis factor and soluble IL-2 receptor, implicating inflammatory responses and T cell activation as causes of the eosinophil activation. By contrast, the eosinophil induction did not appear to be part of a Th2-like response. Eosinophil granule proteins may be important in both control of malaria infection and the pathogenesis of severe malaria.