Fine specificity of the B-cell epitopes recognized in HIV-1 NEF by human sera.

We have previously used partially overlapping synthetic nonapeptides to characterize the human natural antibody response against HIV-1 negative regulatory factor (NEF), and identified nine 5 to 13 amino acid long regions that were recognized by sera of HIV-1-infected individuals. In this report we define the minimal size of these epitopes with the use of shorter, from 3 to 8 amino acid long partially overlapping peptides covering the complete sequence of the previously identified reacting regions and the N- and C-terminal flanking sequences. We also introduce a new method for the analysis of the reactivities obtained with peptides of different lengths. In six of the antigenic regions the epitopes were found to be noncontiguous and to consist of multiple, down to three amino acid long separate reactive stretches (epitope 1: WSK, VGW, TVRERMRR; epitope 3A: PLRPM, SHFLK; epitope 3B: SQRRQD, DLW; epitope 3C: IYHT, QGYFPDWQN; epitope 4: SLL, VSL; epitope 5: EVLEWRFDSR, VAR). Three epitopes were clearly linear (epitope 2: CAWLE; epitope 3D: LTFGWC; epitope 6: PEYF). Interestingly, five of the minimized B-cell epitopes (1, 3A, 3C, 3D, 5) recognized by human sera overlap totally or partly with the previously identified T-cell epitopes in HIV-1 NEF. Also, only three of the epitopes (3C, 3D, 5) were in a computer-based homology search shown to contain strictly NEF-specific sequences.     

Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20-year follow-up study

Background Previous studies suggest an association between an altered lipoprotein profile and atopy. The association has been hypothesized to be due to alterations in the dietary fat intake, a factor possibly contributing to the increase of allergic diseases in industrialized countries. Objective We aimed at assessing whether there is an association between the serum lipid levels in infancy and subsequent development of allergic symptoms in childhood and adolescence. Methods A cohort of 200 unselected newborns was prospectively followed up from birth to age 20 years (from 1981 to 2002) with repeated measurements of total cholesterol from birth and throughout the first year of life. The subjects were re‐examined at the ages of 5, 11 and 20 years, with assessment of the occurrence of allergic symptoms, skin prick testing (SPT) and measurement of total IgE and of the total, high‐ and low‐density lipoprotein cholesterol. Results Children and adolescents with allergic symptoms, SPT positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the non‐atopic subjects. The difference was not detectable in cord blood, but became significant from age 2 months onward. Conclusion The inverse association between the cholesterol level in infancy and subsequent manifestations of atopy seems not to be due to atopy‐related dietary alterations, because it was already present in early infancy, when virtually all the infants were on a similar diet, i.e. on exclusive breastfeeding.     

Antibodies to retroviral proteins in autoimmune connective tissue disease. Relation to clinical manifestations and ribonucleoprotein autoantibodies

Objective. To study the relationship between antibodies that recognize human retroviral proteins and the presence of clinical features and ribonucleoprotein antibodies in patients with autoimmune connective tissue diseases (CTDs). Methods. Antibodies against native human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia/lymphoma virus type I, recombinant HIV-1 Nef protein, and ribonucleoprotein antigens were determined by immunoblot of sera from 65 prospectively studied patients with definite or suspected CTDs of autoimmune type. Results. Antibodies to retroviral proteins (ARP), most frequently to HIV Gag proteins p55 and p24, were found in 64% of 22 patients with systemic lupus erythematosus (SLE), in 63% of 8 patients with discoid LE (DLE), in 75% of 8 patients with mixed connective tissue disease (MCTD), and in 26% of 19 individuals with chronic biologically false-positive (CBFP) seroreactions, but not in 8 patients with subacute cutaneous lupus erythematosus. No clear correlation of ARP with antibodies to any specific small nuclear RNP antigen was observed. The most striking finding was that recurrent infections, both in LE patients and in those with CBFP reactions and widespread, acral discoid skin lesions, occurred significantly more often in ARP-positive patients. Conclusion. The occurrence of antibodies reacting with human retroviral proteins is associated with severe skin lesions and recurrent infections in SLE, DLE, and MCTD patients, and with a disposition toward developing systemic disease in CBFP reactors.     

Oral candidal infection as a sign of HIV infection in homosexual men

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.     

Spatial working memory function in twins with schizophrenia and bipolar disorder.

BACKGROUND: Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proband among the unaffected co-twins of schizophrenic patients. Here, we evaluated whether such deficits might also mark genetic susceptibility to bipolar disorder. METHODS: The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. RESULTS: Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures. CONCLUSIONS: Our findings support the hypothesis that impairment in spatial working memory might effectively reflect an expression of genetic liability to schizophrenia but less clearly to bipolar disorder.     

No evidence for true HTLV-I or HIV-1 antibodies in Finnish Lapps

Previous seroepidemiologic studies have suggested that in addition to certain subtropical and tropical parts of the world, human T cell leukemia virus type I (HTLV-I) may be endemic in the arctic regions, too. We studied 111 sera collected from original inhabitants of Finnish Lapland with ELISA and Western blot analysis for antibodies to HTLV-I and human immunodeficiency virus type 1 (HIV-1). No true positive sera for either virus were found in the confirmatory Western blot assays, albeit 6 and 2%, respectively, were positive in the screening ELISA assays. Despite the small sample size this survey does not support the hypothesis that HTLV-I would be endemic in the Arctic.     

Extralaryngeal HPV infections in male patients with adult-onset laryngeal papillomatosis

Adult-onset laryngeal papillomatosis is a frequently relapsing disease affecting especially males. We studied the history and prevalence of extralaryngeal HPV infections in these patients to find out their susceptibility to HPV. Of adult-onset laryngeal papilloma male patients treated at Helsinki University Central Hospital over 25 years, we examined 50 for clinical findings, examined Pap and cytological samples from the oral mucosa and urethra and biopsied HPV-suspect lesions. Fifteen female sexual partners underwent gynecological examinations. The history of HPV-associated diseases was also determined from age- and sex-matched control subjects. Of the patients, 16% (8) had a history of genital warts and of the controls, 12.5% (6 of 48). A history of skin warts was more common in patients. Their prevalence of genital warts was higher (3 of 50, 6%) than in the general population (1%, earlier study). Prevalence of oral HPV DNA was 8% (4 of 50). Patients sexual habits were unexceptional except for an over-representation of high-frequency orogenital sex initiated at a mean of 9.7 years before diagnosis. However, a lack of orogenital contact did not protect them from severe laryngeal disease. Patients with adult-onset laryngeal papillomatosis seem to be prone to HPV infections. Primary laryngeal HPV infection in adolescence may remain latent, requiring cofactors to develop into the clinical disease.Part of this information was presented at the Fourth Congress of the European Laryngological Society in Brussels, Belgium, 5–7 September 2002. Informed consent was obtained from individuals, and the human experimentation guidelines of Helsinki University Central Hospital were followed. The study was approved by the Ethical Review Board of the Helsinki and Uusimaa University Hospital District.     

Clinical phenotype of schizophrenia in a Finnish isolate

We identified all cases in Finland (population of 5 million) with a diagnosis of schizophrenia born between 1940 and 1969, using four national computerised registers with high reliability. A sample of 397 families was identified in a genetically homogeneous internal isolate (population of 18,000) in northeastern Finland with high prevalence for schizophrenia and an LOD score of 3.8 in chromosome 1. Our aim was to examine with Operational Criteria Checklist for Psychotic Illness (OCCPI) factor analysis the psychotic and affective signs and symptoms of schizophrenia in this genetically homogeneous population, and compare them with findings from individuals with schizophrenia from multiplex families from the whole country. After collecting all original case notes, we made DSM-IV consensus diagnoses and completed OCCPI ratings on a lifetime basis. For the factor analysis, we accepted 190 patients with a diagnosis of schizophrenia. In addition, 466 schizophrenia patients from 147 multiplex families from the whole country were included in the analysis. The OCCPI factor analysis resulted in four factors: "delusions and hallucinations" and "negative" factors, plus two affective ("manic" and "depressive") factors. We compared the pattern of symptoms among three patient groups: isolate patients who were the only affected individuals in their family, isolate patients who had affected family members, and patients from the whole country with affected family members. We found no clear differences among these groups. However, there were significant differences in the frequency of individual OCCPI items between the study groups. Findings in this schizophrenia OCCPI phenotype study suggest that the clinical picture of schizophrenia in a genetically isolated and homogeneous population closely resembles our nationwide findings in Finland.     

Phyto-oestrogen database of foods and average intake in Finland

Information on phyto-oestrogen intake in various populations has been scanty until now, primarily because data on the content of these compounds in foods were lacking. We report here on expansion of the Finnish National Food Composition Database (Fineli) with values for the plant lignans matairesinol and secoisolariciresinol and the isoflavones daidzein and genistein. The values, expressed as aglycones, were based on food analyses (mainly GC-MS) or imputed from analytical data for 180 foods for lignans and 160 foods for isoflavones; additionally, over 1000 values were derived from the recipe database of Fineli. Average intake of these phyto-oestrogens was calculated using food consumption data of the National Dietary Survey FINDIET 1997, which was carried out in a random sample of the adult population in five areas in Finland. The dietary data were collected by 24 h recall =2862). The mean lignan intake was 434 (standard deviation (SD) 1575) microg/d and the mean isoflavone intake was 788 (SD 673) microg/d. Women had a higher lignan density (microg lignans/MJ) in their diet than men (P<0.05). Men had a higher mean daily isoflavone intake, 902 (SD 368) microg, than women, 668 (SD 963) microg (P<0.05). The sources of lignans were many: seeds, cereals, fruit, berries and vegetables. The main sources of isoflavones appeared to be processed meat products/sausages containing soya as an ingredient, and legumes as such. The average intake of lignans and isoflavones in Finland seems to be low, but intake varies throughout the population.